RESUMO
To survive, animals need to balance their exploratory drive with their need for safety. Subcortical circuits play an important role in initiating and modulating movement based on external demands and the internal state of the animal; however, how motivation and onset of locomotion are regulated remain largely unresolved. Here, we show that a glutamatergic pathway from the medial septum and diagonal band of Broca (MSDB) to the ventral tegmental area (VTA) controls exploratory locomotor behavior in mice. Using a self-supervised machine learning approach, we found an overrepresentation of exploratory actions, such as sniffing, whisking, and rearing, when this projection is optogenetically activated. Mechanistically, this role relies on glutamatergic MSDB projections that monosynaptically target a subset of both glutamatergic and dopaminergic VTA neurons. Taken together, we identified a glutamatergic basal forebrain to midbrain circuit that initiates locomotor activity and contributes to the expression of exploration-associated behavior.
Assuntos
Comportamento Exploratório , Área Tegmentar Ventral , Camundongos , Animais , Área Tegmentar Ventral/fisiologia , Neurônios Dopaminérgicos/metabolismo , MotivaçãoRESUMO
When we interact with the environment around us, we are sometimes active participants, making directed physical motor movements and other times only mentally engaging with our environment, taking in sensory information and internally planning our next move without directed physical movement. Traditionally, cortical motor regions and key subcortical structures such as the cerebellum have been tightly linked to motor initiation, coordination, and directed motor behavior. However, recent neuroimaging studies have noted the activation of the cerebellum and wider cortical networks specifically during various forms of motor processing, including the observations of actions and mental rehearsal of movements through motor imagery. This phenomenon of cognitive engagement of traditional motor networks raises the question of how these brain regions are involved in the initiation of movement without physical motor output. Here, we will review evidence for distributed brain network activation during motor execution, observation, and imagery in human neuroimaging studies as well as the potential for cerebellar involvement specifically in motor-related cognition. Converging evidence suggests that a common global brain network is involved in both movement execution and motor observation or imagery, with specific task-dependent shifts in these global activation patterns. We will further discuss underlying cross-species anatomical support for these cognitive motor-related functions as well as the role of cerebrocerebellar communication during action observation and motor imagery.
RESUMO
Functional hemispheric lateralization is a basic principle of brain organization. In the auditory domain, the right auditory cortex (AC) determines the pitch direction of continuous auditory stimuli whereas the left AC discriminates gaps in these stimuli. The involved functional interactions between the two sides, mediated by commissural connections, are poorly understood. Here, we selectively disrupted the interhemispheric cross talk from the left to the right primary AC and vice versa using chromophore-targeted laser-induced apoptosis of the respective projection neurons, which make up 6-17% of all AC neurons in Layers III, V, and VI. Following photolysis, male gerbils were trained in a first experimental set to discriminate between rising and falling frequency-modulated (FM) tone sweeps. The acquisition of the task was significantly delayed in lesioned animals of either lesion direction. However, the final discrimination performance and hit rate was lowest for animals with left-side lesioned commissural neurons, demonstrating that also information from the left AC is relevant for FM direction learning. Photolysis after successful learning did not affect the retrieval of the learned task, indicating that the disruption during learning was not because of a general functional impairment. In a second experimental set, the gerbil's ability to detect and discriminate small silent gaps of varying length within FM sweeps was tested. This ability was also preserved after interhemispheric disruption. Taken together, interhemispheric communication between the left and right AC is important for the acquisition of FM tone direction learning but not for its retrieval and for gap detection and gap duration discrimination.SIGNIFICANCE STATEMENT Hemispheric lateralization of neuronal functions such as speech and music processing in humans are common throughout the brain; however, the involved interhemispheric interactions are ill-defined. Here, we show that the selective photolytic disruption of auditory cortical commissural connections in rodents impairs the acquisition but not retrieval of a frequency-modulated tone direction discrimination task. The final discrimination performance and hit rate was lowest for animals with lesioned left-to-right-side projections; thus, although right auditory cortex is dominant, left auditory cortex is also relevant for learning this task. The detection and discrimination of small gaps within the tone sweeps remain intact, suggesting a pathway for the processing of these temporal structures, which could be independent from the lesioned interhemispheric cross talk.
Assuntos
Córtex Auditivo , Aprendizagem por Discriminação , Estimulação Acústica , Animais , Córtex Auditivo/fisiologia , Aprendizagem por Discriminação/fisiologia , Gerbillinae/fisiologia , Masculino , Discriminação da Altura TonalRESUMO
In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. The impact of the ECM on translaminar dynamics during cortical circuit processing is still not understood. Here, we removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase). Using laminar current-source density (CSD) analysis, we found layer-specific changes of the spatiotemporal synaptic patterns with increased cross-columnar integration and simultaneous weakening of early local sensory input processing within infragranular layers Vb. These changes had an oscillatory fingerprint within beta-band (25-36 Hz) selectively within infragranular layers Vb. To understand the laminar interaction dynamics after ECM digestion, we used time-domain conditional Granger causality (GC) measures to identify the increased drive of supragranular layers towards deeper infragranular layers. These results showed that ECM degradation altered translaminar cortical network dynamics with a stronger supragranular lead of the columnar response profile.
Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva , Potenciais Evocados Auditivos , Matriz Extracelular/fisiologia , Animais , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/metabolismo , Vias Auditivas/fisiologia , Percepção Auditiva/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Gerbillinae , Audição , Hialuronoglucosaminidase/administração & dosagem , Injeções , Masculino , Fatores de TempoRESUMO
As we move through the environment we experience constantly changing sensory input that must be merged with our ongoing motor behaviors - creating dynamic interactions between our sensory and motor systems. Active behaviors such as locomotion generally increase the sensory-evoked neuronal activity in visual and somatosensory cortices, but evidence suggests that locomotion largely suppresses neuronal responses in the auditory cortex. However, whether this effect is ubiquitous across different anatomical regions of the auditory cortex is largely unknown. In mice, auditory association fields such as the dorsal auditory cortex (AuD), have been shown to have different physiological response properties, protein expression patterns, and cortical as well as subcortical connections, in comparison to primary auditory regions (A1) - suggesting there may be important functional differences. Here we examined locomotion-related modulation of neuronal activity in cortical layers â of AuD and A1 using two-photon Ca2+ imaging in head-fixed behaving mice that are able to freely run on a spherical treadmill. We determined the proportion of neurons in these two auditory regions that show enhanced and suppressed sensory-evoked responses during locomotion and quantified the depth of modulation. We found that A1â¯shows more suppression and AuD more enhanced responses during locomotion periods. We further revealed differences in the circuitry between these auditory regions and motor cortex, and found that AuD is more highly connected to motor cortical regions. Finally, we compared the cell-type specific locomotion-evoked modulation of responses in AuD and found that, while subpopulations of PV-expressing interneurons showed heterogeneous responses, the population in general was largely suppressed during locomotion, while excitatory population responses were generally enhanced in AuD. Therefore, neurons in primary and dorsal auditory fields have distinct response properties, with dorsal regions exhibiting enhanced activity in response to movement. This functional distinction may be important for auditory processing during navigation and acoustically guided behavior.
Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/fisiologia , Locomoção/fisiologia , Neurônios/fisiologia , Animais , Córtex Auditivo/química , Córtex Auditivo/citologia , Feminino , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neurônios/químicaRESUMO
The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways. The cerebellar hemispheres were the major target of resulting disynaptic mossy fiber terminals, but we also found at least sparse cerebrocerebellar projections to every lobule of the cerebellum. Notably, projections originating from association cortex resulted in less laterality than primary sensory/motor cortices. Within molecularly defined cerebellar modules we found spatial overlap of mossy fiber terminals, originating from functionally distinct cortical areas, within crus I, paraflocculus, and vermal regions IV/V and VI - highlighting these regions as potential hubs for multimodal cortical influence.
Assuntos
Cerebelo/anatomia & histologia , Cérebro/anatomia & histologia , Vias Neurais/anatomia & histologia , Animais , Tronco Encefálico/anatomia & histologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Rastreamento Neuroanatômico/métodos , Ponte/anatomia & histologiaRESUMO
The potential for neuronal representations of external stimuli to be modified by previous experience is critical for efficient sensory processing and improved behavioral outcomes. To investigate how repeated exposure to a visual stimulus affects its representation in mouse primary visual cortex (V1), we performed two-photon calcium imaging of layer 2/3 neurons and assessed responses before, during, and after the presentation of a repetitive stimulus over 5 consecutive days. We found a stimulus-specific enhancement of the neuronal representation of the repetitively presented stimulus when it was associated with a reward. This was observed both after mice actively learned a rewarded task and when the reward was randomly received. Stimulus-specific enhanced representation resulted both from neurons gaining selectivity and from increased response reliability in previously selective neurons. In the absence of reward, there was either no change in stimulus representation or a decreased representation when the stimulus was viewed at a fixed temporal frequency. Pairing a second stimulus with a reward led to a similar enhanced representation and increased discriminability between the equally rewarded stimuli. Single-neuron responses showed that separate subpopulations discriminated between the two rewarded stimuli depending on whether the stimuli were displayed in a virtual environment or viewed on a single screen. We suggest that reward-associated responses enable the generalization of enhanced stimulus representation across these V1 subpopulations. We propose that this dynamic regulation of visual processing based on the behavioral relevance of sensory input ultimately enhances and stabilizes the representation of task-relevant features while suppressing responses to non-relevant stimuli.
Assuntos
Recompensa , Córtex Visual/fisiologia , Água , Animais , Ingestão de Líquidos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , OrientaçãoRESUMO
Multisensory integration in primary auditory (A1), visual (V1), and somatosensory cortex (S1) is substantially mediated by their direct interconnections and by thalamic inputs across the sensory modalities. We have previously shown in rodents (Mongolian gerbils) that during postnatal development, the anatomical and functional strengths of these crossmodal and also of sensory matched connections are determined by early auditory, somatosensory, and visual experience. Because supragranular layer III pyramidal neurons are major targets of corticocortical and thalamocortical connections, we investigated in this follow-up study how the loss of early sensory experience changes their dendritic morphology. Gerbils were sensory deprived early in development by either bilateral sciatic nerve transection at postnatal day (P) 5, ototoxic inner hair cell damage at P10, or eye enucleation at P10. Sholl and branch order analyses of Golgi-stained layer III pyramidal neurons at P28, which demarcates the end of the sensory critical period in this species, revealed that visual and somatosensory deprivation leads to a general increase of apical and basal dendritic branching in A1, V1, and S1. In contrast, dendritic branching, particularly of apical dendrites, decreased in all three areas following auditory deprivation. Generally, the number of spines, and consequently spine density, along the apical and basal dendrites decreased in both sensory deprived and non-deprived cortical areas. Therefore, we conclude that the loss of early sensory experience induces a refinement of corticocortical crossmodal and other cortical and thalamic connections by pruning of dendritic spines at the end of the critical period. Based on present and previous own results and on findings from the literature, we propose a scenario for multisensory development following early sensory loss.
Assuntos
Córtex Auditivo/fisiologia , Espinhas Dendríticas/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia , Privação Sensorial/fisiologia , Visão Ocular/fisiologia , Córtex Visual/fisiologia , Animais , Córtex Auditivo/citologia , Dendritos/fisiologia , Gerbillinae , Células Piramidais/citologia , Córtex Visual/citologiaRESUMO
Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long-term memory formation is scarce. Our previous pharmacological studies on cortex-dependent frequency-modulated tone-sweep discrimination learning of Mongolian gerbils showed that auditory-cortical D1/5 -dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5 -dopamine receptors and ß-adrenoceptors, we hypothesised a role of ß-adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the ß1/2 -adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post-session time window. When applied to the auditory cortex 1 day before initial conditioning, ß1 -adrenoceptor-antagonising and ß1 -adrenoceptor-stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas ß2 -selective drugs were ineffective. In contrast, single-sweep detection learning was normal after propranolol infusion. By immunohistochemistry, ß1 - and ß2 -adrenoceptors were identified on the neuropil and somata of pyramidal and non-pyramidal neurons of the gerbil auditory cortex. The present findings suggest that ß-adrenergic signalling in the auditory cortex has task-related importance for discrimination learning of complex sounds: as previously shown for D1/5 -dopamine receptor signalling, ß-adrenoceptor activity supports long-term memory consolidation and reconsolidation; additionally, tonic input through ß1 -adrenoceptors may control mechanisms permissive for memory acquisition.
Assuntos
Córtex Auditivo/fisiologia , Aprendizagem por Discriminação/fisiologia , Memória/fisiologia , Receptores Adrenérgicos beta 1/fisiologia , Receptores Adrenérgicos beta 2/fisiologia , Estimulação Acústica , Agonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Animais , Gerbillinae , Masculino , Propranolol/administração & dosagemRESUMO
During aging, human response times (RTs) to unisensory and crossmodal stimuli decrease. However, the elderly benefit more from crossmodal stimulus representations than younger people. The underlying short-latency multisensory integration process is mediated by direct crossmodal connections at the level of primary sensory cortices. We investigate the age-related changes of these connections using a rodent model (Mongolian gerbil), retrograde tracer injections into the primary auditory (A1), somatosensory (S1), and visual cortex (V1), and immunohistochemistry for markers of apoptosis (Caspase-3), axonal plasticity (Growth associated protein 43, GAP 43), and a calcium-binding protein (Parvalbumin, PV). In adult animals, primary sensory cortices receive a substantial number of direct thalamic inputs from nuclei of their matched, but also from nuclei of non-matched sensory modalities. There are also direct intracortical connections among primary sensory cortices and connections with secondary sensory cortices of other modalities. In very old animals, the crossmodal connections strongly decrease in number or vanish entirely. This is likely due to a retraction of the projection neuron axonal branches rather than ongoing programmed cell death. The loss of crossmodal connections is also accompanied by changes in anatomical correlates of inhibition and excitation in the sensory thalamus and cortex. Together, the loss and restructuring of crossmodal connections during aging suggest a shift of multisensory processing from primary cortices towards other sensory brain areas in elderly individuals.
RESUMO
The nervous system integrates information from multiple senses. This multisensory integration already occurs in primary sensory cortices via direct thalamocortical and corticocortical connections across modalities. In humans, sensory loss from birth results in functional recruitment of the deprived cortical territory by the spared senses but the underlying circuit changes are not well known. Using tracer injections into primary auditory, somatosensory, and visual cortex within the first postnatal month of life in a rodent model (Mongolian gerbil) we show that multisensory thalamocortical connections emerge before corticocortical connections but mostly disappear during development. Early auditory, somatosensory, or visual deprivation increases multisensory connections via axonal reorganization processes mediated by non-lemniscal thalamic nuclei and the primary areas themselves. Functional single-photon emission computed tomography of regional cerebral blood flow reveals altered stimulus-induced activity and higher functional connectivity specifically between primary areas in deprived animals. Together, we show that intracortical multisensory connections are formed as a consequence of sensory-driven multisensory thalamocortical activity and that spared senses functionally recruit deprived cortical areas by an altered development of sensory thalamocortical and corticocortical connections. The functional-anatomical changes after early sensory deprivation have translational implications for the therapy of developmental hearing loss, blindness, and sensory paralysis and might also underlie developmental synesthesia.
Assuntos
Mapeamento Encefálico , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Sensação/fisiologia , Córtex Somatossensorial/fisiologia , Núcleos Talâmicos/fisiologia , Estimulação Acústica , Fatores Etários , Animais , Proteínas do Domínio Duplacortina , Feminino , Proteína GAP-43/metabolismo , Gerbillinae , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Rede Nervosa/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Neuropeptídeos/metabolismo , Estimulação Luminosa , Privação Sensorial , Córtex Somatossensorial/diagnóstico por imagem , Estilbamidinas/metabolismo , Tecnécio Tc 99m Exametazima/farmacocinética , Núcleos Talâmicos/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Multisensory integration does not only recruit higher-level association cortex, but also low-level and even primary sensory cortices. Here, we will describe and quantify two types of anatomical pathways, a thalamocortical and a corticocortical that possibly underlie short-latency multisensory integration processes in the primary auditory (A1), somatosensory (S1), and visual cortex (V1). Results were obtained from Mongolian gerbils, a common model-species in neuroscience, using simultaneous injections of different retrograde tracers into A1, S1, and V1. Several auditory, visual, and somatosensory thalamic nuclei project not only to the primary sensory area of their own (matched) but also to areas of other (non-matched) modalities. The crossmodal output ratios of these nuclei, belonging to both core and non-core sensory pathways, vary between 0.4 and 63.5 % of the labeled neurons. Approximately 0.3 % of the sensory thalamic input to A1, 5.0 % to S1, and 2.1 % to V1 arise from non-matched nuclei. V1 has most crossmodal corticocortical connections, projecting strongest to S1 and receiving a similar amount of moderate inputs from A1 and S1. S1 is mainly interconnected with V1. A1 has slightly more projections to V1 than S1, but gets just faint inputs from there. Concerning the layer-specific distribution of the retrogradely labeled somata in cortex, V1 provides the most pronounced feedforward-type outputs and receives (together with S1) most pronounced feedback-type inputs. In contrast, A1 has most pronounced feedback-type outputs and feedforward-type inputs in this network. Functionally, the different sets of thalamocortical and corticocortical connections could underlie distinctive types of integration mechanisms for different modality pairings.