RESUMO
The medial prefrontal cortex (mPFC) contains populations of GABAergic interneurons that play different roles in cognition and emotion. Their local and long-range inputs are incompletely understood. We used monosynaptic rabies viral tracers in combination with fluorescence micro-optical sectioning tomography to generate a whole-brain atlas of direct long-range inputs to GABAergic interneurons in the mPFC of male mice. We discovered that three subtypes of GABAergic interneurons in two areas of the mPFC are innervated by same upstream areas. Input from subcortical upstream areas includes cholinergic neurons from the basal forebrain and serotonergic neurons (which co-release glutamate) from the raphe nuclei. Reconstruction of single-neuron morphology revealed novel substantia innominata-anteromedial thalamic nucleus-mPFC and striatum-anteromedial thalamic nucleus-mPFC circuits. Based on the projection logic of individual neurons, we classified cortical and hippocampal input neurons into several types. This atlas provides the anatomical foundation for understanding the functional organization of the mPFC.
Assuntos
Mapeamento Encefálico/métodos , Interneurônios/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/citologia , Ácido gama-Aminobutírico/fisiologia , Animais , Contagem de Células , Hipocampo/citologia , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Nervoso Parassimpático/citologia , Sistema Nervoso Parassimpático/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/citologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Neurônios Serotoninérgicos/fisiologia , Tálamo/citologia , Tálamo/fisiologiaRESUMO
The thalamus is 1 of 4 major divisions of the forebrain and is usually subdivided into epithalamus, dorsal thalamus, and ventral thalamus. The 39 gray matter regions comprising the large dorsal thalamus project topographically to the cerebral cortex, whereas the much smaller epithalamus (2 regions) and ventral thalamus (5 regions) characteristically project subcortically. Before analyzing extrinsic inputs and outputs of the thalamus, here, the intrinsic connections among all 46 gray matter regions of the rat thalamus on each side of the brain were expertly collated and subjected to network analysis. Experimental axonal pathway-tracing evidence was found in the neuroanatomical literature for the presence or absence of 99% of 2,070 possible ipsilateral connections and 97% of 2,116 possible contralateral connections; the connection density of ipsilateral connections was 17%, and that of contralateral connections 5%. One hub, the reticular thalamic nucleus (of the ventral thalamus), was found in this network, whereas no high-degree rich club or clear small-world features were detected. The reticular thalamic nucleus was found to be primarily responsible for conferring the property of complete connectedness to the intrathalamic network in the sense that there is, at least, one path of finite length between any 2 regions or nodes in the network. Direct comparison with previous investigations using the same methodology shows that each division of the forebrain (cerebral cortex, cerebral nuclei, thalamus, hypothalamus) has distinct intrinsic network topological organization. A future goal is to analyze the network organization of connections within and among these 4 divisions of the forebrain.
Assuntos
Vias Neurais/anatomia & histologia , Prosencéfalo/anatomia & histologia , Núcleos Talâmicos/anatomia & histologia , Tálamo/anatomia & histologia , Animais , Bases de Dados como Assunto , Feminino , Masculino , Vias Neurais/fisiologia , Prosencéfalo/fisiologia , Ratos , Núcleos Talâmicos/fisiologia , Tálamo/fisiologiaRESUMO
The ability of the brain to process sensory information relies on both ascending and descending sets of projections. Until recently, the only way to study these two systems and how they interact has been with the use of in vivo preparations. Major advances have been made with acute brain slices containing the thalamocortical and cortico-thalamic pathways in the somatosensory, visual, and auditory systems. With key refinements to our recent modification of the auditory thalamocortical slice(1), we are able to more reliably capture the projections between most of the major auditory midbrain and forebrain structures: the inferior colliculus (IC), medial geniculate body (MGB), thalamic reticular nucleus (TRN), and the auditory cortex (AC). With portions of all these connections retained, we are able to answer detailed questions that complement the questions that can be answered with in vivo preparations. The use of flavoprotein autofluorescence imaging enables us to rapidly assess connectivity in any given slice and guide the ensuing experiment. Using this slice in conjunction with recording and imaging techniques, we are now better equipped to understand how information processing occurs at each point in the auditory forebrain as information ascends to the cortex, and the impact of descending cortical modulation. 3-D printing to build slice chamber components permits double-sided perfusion and broad access to networks within the slice and maintains the widespread connections key to fully utilizing this preparation.
Assuntos
Mesencéfalo/anatomia & histologia , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Impressão Tridimensional , Prosencéfalo/anatomia & histologia , Animais , Corpos Geniculados/anatomia & histologia , Colículos Inferiores/anatomia & histologia , Camundongos , Tálamo/anatomia & histologiaRESUMO
Naturally occurring cell death is essential to the development of the mammalian nervous system. Although the importance of developmental cell death has been appreciated for decades, there is no comprehensive account of cell death across brain areas in the mouse. Moreover, several regional sex differences in cell death have been described for the ventral forebrain and hypothalamus, but it is not known how widespread the phenomenon is. We used immunohistochemical detection of activated caspase-3 to identify dying cells in the brains of male and female mice from postnatal day (P) 1 to P11. Cell death density, total number of dying cells, and regional volume were determined in 16 regions of the hypothalamus and ventral forebrain (the anterior hypothalamus, arcuate nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus, and ventromedial nucleus of the hypothalamus; the basolateral, central, and medial amygdala; the lateral and principal nuclei of the bed nuclei of the stria terminalis; the caudate-putamen; the globus pallidus; the lateral septum; and the islands of Calleja). All regions showed a significant effect of age on cell death. The timing of peak cell death varied between P1 to P7, and the average rate of cell death varied tenfold among regions. Several significant sex differences in cell death and/or regional volume were detected. These data address large gaps in the developmental literature and suggest interesting region-specific differences in the prevalence and timing of cell death in the hypothalamus and ventral forebrain.
Assuntos
Envelhecimento/fisiologia , Morte Celular/fisiologia , Hipotálamo/anatomia & histologia , Hipotálamo/citologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/citologia , Animais , Atlas como Assunto , Calbindinas/metabolismo , Caspase 3/metabolismo , Ativação Enzimática/fisiologia , Feminino , Hipotálamo/crescimento & desenvolvimento , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prosencéfalo/crescimento & desenvolvimento , Caracteres Sexuais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/fisiologiaRESUMO
The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initial evidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state.
Assuntos
Nível de Alerta/fisiologia , Transtornos da Consciência/patologia , Estado de Consciência/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/patologia , Adulto , Autopsia , Tronco Encefálico/anatomia & histologia , Tronco Encefálico/patologia , Cadáver , Imagem de Tensor de Difusão , Dissecação , Feminino , Humanos , Hipotálamo/anatomia & histologia , Hipotálamo/patologia , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neuroanatomia , Neurotransmissores/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/patologia , Tratos Piramidais/anatomia & histologia , Tratos Piramidais/patologia , Tratos Piramidais/fisiologia , Tálamo/anatomia & histologia , Tálamo/patologiaRESUMO
The "ascending reticular activating system" theory proposed that neurons in the upper brainstem reticular formation projected to forebrain targets that promoted wakefulness. More recent formulations have emphasized that most neurons at the pontomesencephalic junction that participate in these pathways are actually in monoaminergic and cholinergic cell groups. However, cell-specific lesions of these cell groups have never been able to reproduce the deep coma seen after acute paramedian midbrain lesions that transect ascending axons at the caudal midbrain level. To determine whether the cortical afferents from the thalamus or the basal forebrain were more important in maintaining arousal, we first placed large cell-body-specific lesions in these targets. Surprisingly, extensive thalamic lesions had little effect on electroencephalographic (EEG) or behavioral measures of wakefulness or on c-Fos expression by cortical neurons during wakefulness. In contrast, animals with large basal forebrain lesions were behaviorally unresponsive and had a monotonous sub-1-Hz EEG, and little cortical c-Fos expression during continuous gentle handling. We then retrogradely labeled inputs to the basal forebrain from the upper brainstem, and found a substantial input from glutamatergic neurons in the parabrachial nucleus and adjacent precoeruleus area. Cell-specific lesions of the parabrachial-precoeruleus complex produced behavioral unresponsiveness, a monotonous sub-1-Hz cortical EEG, and loss of cortical c-Fos expression during gentle handling. These experiments indicate that in rats the reticulo-thalamo-cortical pathway may play a very limited role in behavioral or electrocortical arousal, whereas the projection from the parabrachial nucleus and precoeruleus region, relayed by the basal forebrain to the cerebral cortex, may be critical for this process.
Assuntos
Nível de Alerta/fisiologia , Vias Neurais/anatomia & histologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiologia , Animais , Comportamento Animal/fisiologia , Eletroencefalografia , Eletromiografia , Agonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Ácido Ibotênico/farmacologia , Masculino , Vias Neurais/patologia , Vias Neurais/fisiologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Sono/fisiologia , Tálamo/anatomia & histologia , Tálamo/efeitos dos fármacos , Tálamo/patologia , Tálamo/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Vigília/fisiologiaRESUMO
Prepulse inhibition (PPI) refers to the reduction in the startle response when a startling stimulus is preceded by a weak prestimulus, and is an endophenotype of deficient sensorimotor gating in several neuropsychiatric disorders. Emerging evidence suggests that norepinephrine (NE) regulates PPI, however, the circuitry involved is unknown. We found recently that stimulation of the locus coeruleus (LC), the primary source of NE to the forebrain, induces a PPI deficit that is a result of downstream NE release. Hence, this study sought to identify LC-innervated forebrain regions that mediate this effect. Separate groups of male Sprague-Dawley rats received a cocktail solution of the α1-NE receptor agonist phenylephrine plus the ß-receptor agonist isoproterenol (equal parts of each; 0, 3, 10, and 30 µg) into subregions of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc), extended amygdala, mediodorsal thalamus (MD-thalamus), or the dorsal hippocampus (DH) before PPI testing. NE agonist infusion into the posterior mPFC, NAcc shell, bed nucleus of the stria terminalis, basolateral amygdala, and the MD-thalamus disrupted PPI, with particularly strong effects in MD-thalamus. Sites in which NE receptor stimulation did not disrupt PPI (anterior mPFC, NAcc core, central amygdala, and DH) did support PPI disruptions with the dopamine D2 receptor agonist quinpirole (0, 10 µg). This pattern reveals new pathways in the regulation of PPI, and suggests that NE transmission within distinct thalamocortical and ventral forebrain networks may subserve the sensorimotor gating deficits that are seen in disorders such as schizophrenia, Tourette syndrome, and post-traumatic stress disorder.
Assuntos
Inibição Neural/fisiologia , Vias Neurais/fisiologia , Norepinefrina/metabolismo , Prosencéfalo/fisiologia , Reflexo de Sobressalto/fisiologia , Filtro Sensorial/fisiologia , Estimulação Acústica/efeitos adversos , Adrenérgicos/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Mapeamento Encefálico , Agonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Interações Medicamentosas , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Inibição Neural/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Prosencéfalo/anatomia & histologia , Prosencéfalo/efeitos dos fármacos , Psicoacústica , Quimpirol/farmacologia , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Filtro Sensorial/efeitos dos fármacosRESUMO
The pontine parabrachial nucleus (PBN) and medullary reticular formation (RF) are hindbrain regions that, respectively, process sensory input and coordinate motor output related to ingestive behavior. Neural processing in each hindbrain site is subject to modulation originating from several forebrain structures including the insular gustatory cortex (IC), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and lateral hypothalamus (LH). The present study combined electrophysiology and retrograde tracing techniques to determine the extent of overlap between neurons within the IC, BNST, CeA and LH that target both the PBN and RF. One fluorescent retrograde tracer, red (RFB) or green (GFB) latex microbeads, was injected into the gustatory PBN under electrophysiological guidance and a different retrograde tracer, GFB or fluorogold (FG), into the ipsilateral RF using the location of gustatory NST as a point of reference. Brain tissue containing each forebrain region was sectioned, scanned using a confocal microscope, and scored for the number of single and double labeled neurons. Neurons innervating the RF only, the PBN only, or both the medullary RF and PBN were observed, largely intermingled, in each forebrain region. The CeA contained the largest number of cells retrogradely labeled after tracer injection into either hindbrain region. For each forebrain area except the IC, the origin of descending input to the RF and PBN was almost entirely ipsilateral. Axons from a small percentage of hindbrain projecting forebrain neurons targeted both the PBN and RF. Target specific and non-specific inputs from a variety of forebrain nuclei to the hindbrain likely reflect functional specialization in the control of ingestive behaviors.
Assuntos
Axônios , Vias Eferentes/anatomia & histologia , Neurônios Eferentes , Ponte/anatomia & histologia , Prosencéfalo/anatomia & histologia , Formação Reticular/anatomia & histologia , Tonsila do Cerebelo/anatomia & histologia , Animais , Córtex Cerebral/anatomia & histologia , Hipotálamo/anatomia & histologia , Masculino , Bulbo/anatomia & histologia , Ratos , Ratos Sprague-Dawley , Núcleos Septais/anatomia & histologiaRESUMO
In the rat cortex, the two non-primary auditory areas, posterodorsal and ventral auditory areas, may constitute the two streams of auditory processing in their distinct projections to the posterior parietal and insular cortices. The posterior parietal cortex is considered crucial for auditory spatial processing and directed attention, while possible auditory function of the insular cortex is largely unclear. In this study, we electrophysiologically delineated an auditory area in the caudal part of the granular insular cortex (insular auditory area, IA) and examined efferent connections of IA with anterograde tracer biocytin to deduce the functional significance of IA. IA projected to the rostral agranular insular cortex, a component of the lateral prefrontal cortex. IA also projected to the adjacent dysgranular insular cortex and the caudal agranular insular cortex and sent feedback projections to cortical layer I of the primary and secondary somatosensory areas. Corticofugal projections terminated in auditory, somatosensory and visceral thalamic nuclei, and the bottom of the thalamic reticular nucleus that could overlap the visceral sector. The ventral part of the caudate putamen, the external cortex of the inferior colliculus and the central amygdaloid nucleus were also the main targets. IA exhibited neural response to transcutaneous electrical stimulation of the forepaw in addition to acoustic stimulation (noise bursts and pure tones). The results suggest that IA subserves diverse functions associated with somatosensory, nociceptive and visceral processing that may underlie sound-driven emotional and autonomic responses. IA, being potentially involved in such extensive cross-modal sensory interactions, could also be an important anatomical node of auditory processing linked to higher neural processing in the prefrontal cortex.
Assuntos
Vias Auditivas/anatomia & histologia , Percepção Auditiva/fisiologia , Córtex Cerebral/anatomia & histologia , Vias Eferentes/anatomia & histologia , Rede Nervosa/anatomia & histologia , Prosencéfalo/anatomia & histologia , Estimulação Acústica , Animais , Vias Auditivas/fisiologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Vias Eferentes/fisiologia , Estimulação Elétrica , Eletrofisiologia , Emoções/fisiologia , Lisina/análogos & derivados , Masculino , Rede Nervosa/fisiologia , Marcadores do Trato Nervoso , Dor/fisiopatologia , Córtex Pré-Frontal/anatomia & histologia , Prosencéfalo/fisiologia , Ratos , Ratos Wistar , Sensação/fisiologia , Fibras Aferentes Viscerais/anatomia & histologia , Fibras Aferentes Viscerais/fisiologiaRESUMO
In rats, whisking behavior is characterized by high-frequency synchronous movements and other stereotyped patterns of bilateral coordination that are rarely seen in the bilateral movements of the limbs. This suggests that the motor systems controlling whisker and limb movements must have qualitative or quantitative differences in their interhemispheric connections. To test this hypothesis, anterograde tracing methods were used to characterize the bilateral distribution of projections from the whisker and forepaw regions in the primary motor (MI) cortex. Unilateral tracer injections in the MI whisker or forepaw regions revealed robust projections to the corresponding MI cortical area in the contralateral hemisphere. Both MI regions project bilaterally to the neostriatum, but the corticostriatal projections from the whisker region are denser and more evenly distributed across both hemispheres than those from the MI forepaw region. The MI whisker region projects bilaterally to several nuclei in the thalamus, whereas the MI forepaw region projects almost exclusively to the ipsilateral thalamus. The MI whisker region sends dense projections to the contralateral claustrum, but those to the ipsilateral claustrum are less numerous. By contrast, the MI forepaw region sends few projections to the claustrum of either hemisphere. Bilateral deposits of different tracers in MI revealed overlapping projections to the neostriatum, thalamus, and claustrum when the whisker regions were injected, but not when the forepaw regions were injected. These results suggest that the bilateral coordination of the whiskers depends, in part, on MI projections to the contralateral neostriatum, thalamus, and claustrum.
Assuntos
Gânglios da Base/anatomia & histologia , Comportamento Exploratório/fisiologia , Córtex Motor/anatomia & histologia , Neostriado/anatomia & histologia , Vias Neurais , Tálamo/anatomia & histologia , Vibrissas/inervação , Animais , Comportamento Animal/fisiologia , Mapeamento Encefálico/métodos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Prosencéfalo/anatomia & histologia , Ratos , Ratos Sprague-DawleyRESUMO
The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguus (NA) by 3 days post-inoculation, PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii, the Botzinger complex, and the parvicellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvicellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggests PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex CNS control over the multi-functional thyroarytenoid muscle.
Assuntos
Músculos Laríngeos/inervação , Neurônios Motores/fisiologia , Prosencéfalo/fisiologia , Animais , Herpesvirus Suídeo 1 , Hipotálamo/fisiologia , Nervos Laríngeos/citologia , Nervos Laríngeos/fisiologia , Masculino , Bulbo/fisiologia , Ponte/fisiologia , Prosencéfalo/anatomia & histologia , Ratos , Ratos Sprague-Dawley , Simpatectomia , Fatores de TempoRESUMO
Steroid hormones, especially estradiol, facilitate reproductive behaviors in male and female rodents and birds. In green anole lizards estradiol facilitates receptivity in females but, unlike in some other species, is not the activating hormone for courtship and copulatory behavior in males. Instead, testicular androgens directly facilitate male courtship and copulation. Yet, activity of the estradiol synthesizing enzyme aromatase is higher in the brain of male than female green anoles, and it is increased during the breeding compared to the non-breeding season. The functional relevance of these differences in local estradiol production is unknown. They might prime the male forebrain to facilitate production of appropriate sexual behaviors, perhaps by modifying morphology of relevant brain regions. In addition, we recently reported increased expression of estrogen receptor alpha (ERalpha) in selected brain regions in females compared to males [Beck LA, Wade J (2009b) Sexually dimorphic estrogen receptor alpha mRNA expression in the preoptic area and ventromedial hypothalamus of green anole lizards. 55:398-403]. Thus, it is possible that the hormone serves to downregulate its receptor in males to inhibit the expression of estradiol-dependent receptive behaviors. To begin to address these ideas, the present study examines the effects of estradiol treatment, sex, and season on forebrain morphology and ERalpha mRNA abundance in three regions important for anole reproductive behavior-the preoptic area, ventromedial amygdala, and ventromedial hypothalamus. While a number of effects of sex and season on forebrain morphology were detected, direct effects of estradiol treatment on these measures were minimal. ERalpha expression was greatest in the ventromedial hypothalamus, and a large female-biased sex difference was detected in this area alone; it resulted from estradiol-treated animals. These results indicate a sex- and region-specific mechanism by which estradiol can modify ERalpha expression in the green anole and could impact the expression of female-typical receptivity.
Assuntos
Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Lagartos/fisiologia , Prosencéfalo/fisiologia , Reprodução/fisiologia , Caracteres Sexuais , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Análise de Variância , Animais , Castração , Contagem de Células , Estradiol/análogos & derivados , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Hipotálamo/anatomia & histologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Hibridização In Situ , Lagartos/anatomia & histologia , Masculino , Tamanho do Órgão , Área Pré-Óptica/anatomia & histologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/efeitos dos fármacos , RNA Mensageiro/metabolismo , RadioimunoensaioRESUMO
BACKGROUND: With the advent of functional magnetic resonance imaging (fMRI) in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. RESULTS: To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. CONCLUSION: The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus), emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex) and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding. Drugs that block vasopressin neurotransmission or enhance serotonin activity suppress activity in this putative neural circuit of aggressive motivation, particularly the anterior thalamic nuclei.
Assuntos
Agressão/psicologia , Encéfalo/fisiologia , Motivação , Rede Nervosa/fisiologia , Administração Oral , Agressão/efeitos dos fármacos , Agressão/fisiologia , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/farmacologia , Hipotálamo/anatomia & histologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/efeitos dos fármacos , Prosencéfalo/anatomia & histologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/fisiologia , Ratos , Ratos Long-Evans , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Tálamo/anatomia & histologia , Tálamo/efeitos dos fármacos , Tálamo/fisiologiaRESUMO
BACKGROUND: Male songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the 'song system' is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS) is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM), show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium. METHODS AND FINDINGS: Using blood oxygen level-dependent (BOLD) fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b. CONCLUSIONS: Based on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory processing stream.
Assuntos
Tentilhões/fisiologia , Imageamento por Ressonância Magnética/métodos , Prosencéfalo/anatomia & histologia , Estimulação Acústica/métodos , Comunicação Animal , Animais , Córtex Auditivo/fisiologia , Vias Auditivas/fisiologia , Processamento de Imagem Assistida por Computador , Masculino , Neurônios/metabolismo , Prosencéfalo/fisiologia , Som , Telencéfalo/fisiologia , Fatores de Tempo , Vocalização Animal/fisiologiaRESUMO
Recent studies have shown the nutrient-sensing systems transmitting nutritive information from the gut to the brain. However neural activity evoked by ingested dietary nutrients has not been investigated adequately. Using functional magnetic resonance imaging, we demonstrated that rat forebrain responded to intragastric administration of glucose, L-glutamate, and NaCl. These dietary nutrients led to a significant activation in the forebrain regions including nucleus accumbens, hypothalamic area, and limbic system with different timings. These data indicate that several forebrain regions have important roles on perception and process of postingestive nutrient information.
Assuntos
Glucose/farmacologia , Ácido Glutâmico/farmacologia , Prosencéfalo/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Animais , Alimentos , Glucose/administração & dosagem , Ácido Glutâmico/administração & dosagem , Hipotálamo/anatomia & histologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Sistema Límbico/anatomia & histologia , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/fisiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Núcleo Accumbens/anatomia & histologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiologia , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio/administração & dosagemRESUMO
Recently, fMRI was introduced in a well-documented animal model for vocal learning, the songbird. Using fMRI and conspecific signals mixed with different levels of broadband noise, we now demonstrate auditory-induced activation representing discriminatory properties of auditory forebrain regions in anesthetized male zebra finches (Taeniopygia guttata). Earlier behavioral tests showed comparable calling responses to the original conspecific song stimulus heard outside and inside the magnet. A significant fMRI response was elicited by conspecific song in the primary auditory thalamo-recipient subfield L2a; in neighboring subareas L2b, L3, and L; and in the rostral part of the higher-order auditory area NCM (caudomedial nidopallium). Temporal BOLD response clustering revealed rostral and caudal clusters that we defined as "cluster Field L" and "cluster NCM", respectively. However, because the actual border between caudal Field L subregions and NCM cannot be seen in the structural MR image and is not precisely reported elsewhere, the cluster NCM might also contain subregion L and the medial extremes of the subregions L2b and L3. Our results show that whereas in cluster Field L the response was not reduced by added noise, in cluster NCM the response was reduced and finally disappeared with increasing levels of noise added to the song stimulus. The activation in cluster NCM was significant for only two experimental stimuli that showed significantly more behavioral responses than the more degraded stimuli, suggesting that the first area within the auditory system where the ability to discern song from masking noise emerges is located in cluster NCM.
Assuntos
Percepção Auditiva/fisiologia , Mapeamento Encefálico , Discriminação Psicológica/fisiologia , Tentilhões/fisiologia , Ruído , Prosencéfalo/irrigação sanguínea , Vocalização Animal/fisiologia , Estimulação Acústica/métodos , Animais , Comportamento Animal , Tentilhões/anatomia & histologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiologiaRESUMO
The forebrain of elasmobranchs is well developed, and in some species the relative brain/body weight is comparable to that in mammals. However, little is known about the organization of major telencephalic pathways. We injected biotinylated dextran amines into the olfactory bulb, lateral pallium, dorsomedial pallium, and the forebrain bundles of the thornback ray, Platyrhinoidis triseriata. Secondary olfactory fibers from the bulb innervate the lateral pallium, the ventral division of the rostral telencephalon and area superficialis basalis. Retrogradely labeled cells were seen exclusively in the lateral periventricular area. The projections of the lateral pallium appeared basically similar to those of the olfactory bulb, but labeling was much denser in the superficial part of area basalis. Some fibers were also seen to innervate the posterior tuberal nucleus. Injections into the dorsomedial pallium revealed a major input from area basalis. Only a few cells were retrogradely labeled in the dorsal thalamus and posterior lateral thalamic nucleus. Major efferents of the dorsomedial pallium appear to reach the contralateral inferior lobe of the hypothalamus and the lateral mesencephalic nucleus. Tracer injections into the forebrain bundles retrogradely labeled many cells in the diencephalon and the mesencephalon and also revealed terminal fields in area superficialis basalis. In addition, a large number of cells were labeled in the dorsomedial pallium. Descending telencephalic fibers innervate heavily the inferior lobes and the lateral mesencephalic nucleus. Our results show that higher order olfactory pathway courses from the lateral pallium through area basalis to the dorsomedial pallium and that ascending non-olfactory input is integrated in area superficialis basalis and the dorsal pallium along with olfactory information, rather than being processed in separate, non-olfactory centers.
Assuntos
Modelos Anatômicos , Vias Neurais/anatomia & histologia , Rajidae/anatomia & histologia , Telencéfalo/anatomia & histologia , Vias Aferentes/anatomia & histologia , Animais , Diencéfalo/anatomia & histologia , Vias Eferentes/anatomia & histologia , Hipotálamo/anatomia & histologia , Mesencéfalo/anatomia & histologia , Bulbo Olfatório/anatomia & histologia , Condutos Olfatórios/anatomia & histologia , Prosencéfalo/anatomia & histologiaRESUMO
Song perception in songbirds, just as music and speech perception in humans, requires processing the spectral and temporal structure found in the succession of song-syllables. Using functional magnetic resonance imaging and synthetic songs that preserved exclusively either the temporal or the spectral structure of natural song, we investigated how vocalizations are processed in the avian forebrain. We found bilateral and equal activation of the primary auditory region, field L. The more ventral regions of field L showed depressed responses to the synthetic songs that lacked spectral structure. These ventral regions included subarea L3, medial-ventral subarea L and potentially the secondary auditory region caudal medial nidopallium. In addition, field L as a whole showed unexpected increased responses to the temporally filtered songs and this increase was the largest in the dorsal regions. These dorsal regions included L1 and the dorsal subareas L and L2b. Therefore, the ventral region of field L appears to be more sensitive to the preservation of both spectral and temporal information in the context of song processing. We did not find any differences in responses to playback of the bird's own song vs other familiar conspecific songs. We also investigated the effect of three commonly used anaesthetics on the blood oxygen level-dependent response: medetomidine, urethane and isoflurane. The extent of the area activated and the stimulus selectivity depended on the type of anaesthetic. We discuss these results in the context of what is known about the locus of action of the anaesthetics, and reports of neural activity measured in electrophysiological experiments.
Assuntos
Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Potenciais Evocados/fisiologia , Tentilhões/fisiologia , Prosencéfalo/fisiologia , Vocalização Animal/fisiologia , Estimulação Acústica , Anestésicos/farmacologia , Animais , Córtex Auditivo/anatomia & histologia , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/fisiologia , Vias Auditivas/anatomia & histologia , Percepção Auditiva/efeitos dos fármacos , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Tentilhões/anatomia & histologia , Imageamento por Ressonância Magnética , Masculino , Percepção da Altura Sonora/efeitos dos fármacos , Percepção da Altura Sonora/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Especificidade da Espécie , Telencéfalo/anatomia & histologia , Telencéfalo/efeitos dos fármacos , Telencéfalo/fisiologia , Percepção do Tempo/efeitos dos fármacos , Percepção do Tempo/fisiologiaRESUMO
This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion.
Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Psicológico , Prosencéfalo/fisiologia , Paladar , Análise de Variância , Animais , Comportamento Animal/fisiologia , Mapeamento Encefálico , Cloreto de Lítio/administração & dosagem , Masculino , Prosencéfalo/anatomia & histologia , Ratos , Ratos Wistar , Sacarina/administração & dosagem , Edulcorantes/administração & dosagemRESUMO
The extreme virilization of the female spotted hyena raises interesting questions with respect to sexual differentiation of the brain and behavior. Females are larger and more aggressive than adult, non-natal males and dominate them in social encounters; their external genitalia also are highly masculinized. In many vertebrates, the arginine vasopressin (VP) innervation of the forebrain, particularly that of the lateral septum, is associated with social behaviors such as aggression and dominance. Here, we used immunohistochemistry to examine the distribution of VP cells and fibers in the forebrains of adult spotted hyenas. We find the expected densely staining VP immunoreactive (VP-ir) neurons in the paraventricular and supraoptic nuclei, as well as an unusually extensive distribution of magnocelluar VP-ir neurons in accessory regions. A small number of VP-ir cell bodies are present in the suprachiasmatic nucleus and bed nucleus of the stria terminalis; however, there are extensive VP-ir fiber networks in presumed projection areas of these nuclei, for example, the subparaventricular zone and lateral septum, respectively. No significant sex differences were detected in the density of VP-ir fibers in any area examined. In the lateral septum, however, marked variability was observed. Intact females exhibited a dense fiber network, as did two of the four males examined; the two other males had almost no VP-ir septal fibers. This contrasts with findings in many other vertebrate species, in which VP innervation of the lateral septum is consistently greater in males than in females.