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1.
Front Neural Circuits ; 16: 863478, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860211

RESUMO

The marmoset (a New World monkey) has recently received much attention as an experimental animal model; however, little is known about the connectivity of limbic regions, including cortical and hippocampal memory circuits, in the marmoset. Here, we investigated the neuronal connectivity of the marmoset, especially focusing on the connectivity between the hippocampal formation and the presubiculum, using retrograde and anterograde tracers (cholera toxin-B subunit and biotin dextran amine). We demonstrated the presence of a direct projection from the CA1 pyramidal cell layer to the deep layers of the presubiculum in the marmoset, which was previously identified in the rabbit brain, but not in the rat. We also found that the cells of origin of the subiculo-presubicular projections were localized in the middle part along the superficial-to-deep axis of the pyramidal cell layer of the distal subiculum in the marmoset, which was similar to that in both rats and rabbits. Our results suggest that, compared to the rat and rabbit brains, connections between the hippocampal formation and presubiculum are highly organized and characteristic in the marmoset brain.


Assuntos
Callithrix , Giro Para-Hipocampal , Animais , Encéfalo , Hipocampo/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Coelhos , Ratos
2.
Nat Commun ; 13(1): 4039, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864121

RESUMO

The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse ("social instigation") resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice. In contrast, inhibition of this pathway did not affect basal levels of aggressive behavior, suggesting that the activity of the LHb-DRN projection is not necessary for the expression of species-typical aggressive behavior, but required for the increase of aggressive behavior resulting from social instigation. Anatomical analysis showed that LHb neurons synapse on non-serotonergic DRN neurons that project to the ventral tegmental area (VTA), and optogenetic activation of the DRN-VTA projection increased aggressive behaviors. Our results demonstrate that the LHb glutamatergic inputs to the DRN promote aggressive arousal induced by social instigation, which contributes to aggressive behavior by activating VTA-projecting non-serotonergic DRN neurons as one of its potential targets.


Assuntos
Núcleo Dorsal da Rafe , Habenula , Agressão/fisiologia , Animais , Nível de Alerta , Núcleo Dorsal da Rafe/fisiologia , Habenula/fisiologia , Masculino , Camundongos , Vias Neurais/fisiologia , Neurônios/metabolismo
3.
Nature ; 607(7919): 521-526, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794480

RESUMO

The direct and indirect pathways of the basal ganglia are classically thought to promote and suppress action, respectively1. However, the observed co-activation of striatal direct and indirect medium spiny neurons2 (dMSNs and iMSNs, respectively) has challenged this view. Here we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and cued actions and, critically, a sustained period of dynamic action suppression. Although movement produced the co-activation of iMSNs and dMSNs in the sensorimotor, dorsolateral striatum (DLS), fibre photometry and photo-identified electrophysiological recordings revealed signatures of functional opponency between the two pathways during action suppression. Notably, optogenetic inhibition showed that DLS circuits were largely engaged to suppress-and not promote-action. Specifically, iMSNs on a given hemisphere were dynamically engaged to suppress tempting contralateral action. To understand how such regionally specific circuit function arose, we constructed a computational reinforcement learning model that reproduced key features of behaviour, neural activity and optogenetic inhibition. The model predicted that parallel striatal circuits outside the DLS learned the action-promoting functions, generating the temptation to act. Consistent with this, optogenetic inhibition experiments revealed that dMSNs in the associative, dorsomedial striatum, in contrast to those in the DLS, promote contralateral actions. These data highlight how opponent interactions between multiple circuit- and region-specific basal ganglia processes can lead to behavioural control, and establish a critical role for the sensorimotor indirect pathway in the proactive suppression of tempting actions.


Assuntos
Corpo Estriado , Modelos Neurológicos , Inibição Neural , Vias Neurais , Neurônios , Animais , Simulação por Computador , Corpo Estriado/citologia , Corpo Estriado/fisiologia , Camundongos , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Optogenética
4.
Neuroimage ; 259: 119441, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35792289

RESUMO

The cytoarchitectonically tripartite organization of the inferior parietal cortex (IPC) into the rostral, the middle and the caudal clusters has been generally ignored when associating different functions to this part of the cortex, resulting in inconsistencies about how IPC is understood. In this study, we investigated the patterns of functional connectivity of the caudal IPC in a task requiring cognitive control, using multiband EPI. This part of the cortex demonstrated functional connectivity patterns dissimilar to a cognitive control area and at the same time the caudal IPC showed negative functional associations with both task-related brain areas and the precuneus cortex, which is active during resting state. We found evidence suggesting that the traditional categorization of different brain areas into either task-related or resting state-related networks cannot accommodate the functions of the caudal IPC. This underlies the hypothesis about a new brain functional category as a modulating cortical area proposing that its involvement in task performance, in a modulating manner, is marked by deactivation in the patterns of functional associations with parts of the brain that are recognized to be involved in doing a task, proportionate to task difficulty; however, its patterns of functional connectivity in some other respects do not correspond to the resting state-related parts of the cortex.


Assuntos
Mapeamento Encefálico , Lobo Parietal , Encéfalo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/fisiologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia
5.
Adv Exp Med Biol ; 1378: 77-86, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35902466

RESUMO

Emotions induce complex patterns of cerebellar activity likely reflecting specific cerebellar modulation and multidimensional integration of the emotional experience, based on context-specific dynamic recruitment of limbic, cognitive, mnesic, and sensorimotor cortico-cerebellar loops. Meta-analyses have reported constant recruitment of lobules VI-VII during basic emotions. Activation of rostral lobules II-VI and lobule VIII may be preferentially in relation to motor responses, whereas rostral and caudal vermal activation may be linked to autonomic regulation and associative learning in conjunction with amygdala. Cognitive integration of emotion may rely, at least, on activation of limbic salience network (automatic bottom-up detection of salient stimulus), default-mode network (memory- and knowledge-based categorization), and central executive network (response selection and emotion regulation). As lobules VI-VII straddle all these intrinsically networks, it could be hypothesized that this part of the neocerebellum constitutes an integrator/modulator hub of the emotion-related limbic and cognitive system.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Emoções/fisiologia , Imageamento por Ressonância Magnética/métodos , Vias Neurais/fisiologia
6.
PLoS Comput Biol ; 18(6): e1010255, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35737720

RESUMO

In situations featuring uncertainty about action-reward contingencies, mammals can flexibly adopt strategies for decision-making that are tuned in response to environmental changes. Although the cortico-basal ganglia thalamic (CBGT) network has been identified as contributing to the decision-making process, it features a complex synaptic architecture, comprised of multiple feed-forward, reciprocal, and feedback pathways, that complicate efforts to elucidate the roles of specific CBGT populations in the process by which evidence is accumulated and influences behavior. In this paper we apply a strategic sampling approach, based on Latin hypercube sampling, to explore how variations in CBGT network properties, including subpopulation firing rates and synaptic weights, map to variability of parameters in a normative drift diffusion model (DDM), representing algorithmic aspects of information processing during decision-making. Through the application of canonical correlation analysis, we find that this relationship can be characterized in terms of three low-dimensional control ensembles within the CBGT network that impact specific qualities of the emergent decision policy: responsiveness (a measure of how quickly evidence evaluation gets underway, associated with overall activity in corticothalamic and direct pathways), pliancy (a measure of the standard of evidence needed to commit to a decision, associated largely with overall activity in components of the indirect pathway of the basal ganglia), and choice (a measure of commitment toward one available option, associated with differences in direct and indirect pathways across action channels). These analyses provide mechanistic predictions about the roles of specific CBGT network elements in tuning the way that information is accumulated and translated into decision-related behavior.


Assuntos
Gânglios da Base , Tálamo , Animais , Gânglios da Base/fisiologia , Cognição , Mamíferos , Vias Neurais/fisiologia , Recompensa , Tálamo/fisiologia , Incerteza
7.
Int J Psychophysiol ; 178: 22-33, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35709946

RESUMO

In a recent study we outlined the link between Intolerance of Uncertainty (IU) and the neural correlates of affective predictions, as constructed by the brain (generation stage) to prepare to relevant stimuli (implementation stage), and update predictive models according to incoming stimuli (updating stage). In this study we further explored whether the brain's functional organization at rest can modulate neural activity elicited within an emotional S1-S2 paradigm as a function of IU and uncertainty of S1-S2 contingencies. We computed resting state functional connectivity (RS-FC) from a 3-min resting period recorded with high density EEG, and we tested whether RS graph theory nodal measures (i.e., strength, clustering coefficient, betweenness centrality) predicted in-task ERP modulation as a function of IU. We found that RS-FC differently predicted in-task ERPs within the generation and updating stages. Higher IU levels were associated to altered RS-FC patterns within both domain-specific (i.e., right superior temporal sulcus) and domain-general regions (i.e., right orbitofrontal cortex), predictive of a reduced modulation of in-task ERPs in the generation and updating stages. This is presumably ascribable to an unbalancing between synchronization and integration within these regions, which may disrupt the exchange of information between top-down and bottom-up pathways. This altered RS-FC pattern may in turn result in the construction of less efficient affective predictions and a reduced ability to deal with contextual uncertainty in individuals high in IU.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Encéfalo/fisiologia , Eletroencefalografia , Humanos , Vias Neurais/fisiologia , Incerteza
8.
Neuroscience ; 496: 83-95, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35710064

RESUMO

Evaluation of stimulus salience is critical for any higher organism, as it allows for prioritizing of vital information, preparation of responses, and formation of valuable memory. The paraventricular nucleus of the thalamus (PVT) has recently been identified as an integrator of stimulus salience but the neurochemical basis and afferent input regarding salience signaling have remained elusive. Here we report that neuropeptide S (NPS) signaling in the PVT is necessary for stimulus salience encoding, including aversive, neutral and reinforcing sensory input. Taking advantage of a striking deficit of both NPS receptor (NPSR1) and NPS precursor knockout mice in fear extinction or novel object memory formation, we demonstrate that intra-PVT injections of NPS can rescue the phenotype in NPS precursor knockout mice by increasing the salience of otherwise low-intensity stimuli, while intra-PVT injections of NPSR1 antagonist in wild type mice partially replicates the knockout phenotype. The PVT appears to provide stimulus salience encoding in a dose- and NPS-dependent manner. PVT NPSR1 neurons recruit the nucleus accumbens shell and structures in the prefrontal cortex and amygdala, which were previously linked to the brain salience network. Overall, these results demonstrate that stimulus salience encoding is critically associated with NPS activity in the PVT.


Assuntos
Núcleos da Linha Média do Tálamo , Neuropeptídeos , Animais , Extinção Psicológica , Medo/fisiologia , Camundongos , Núcleos da Linha Média do Tálamo/fisiologia , Vias Neurais/fisiologia , Núcleo Hipotalâmico Paraventricular , Tálamo/fisiologia
9.
Brain Behav ; 12(7): e2646, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35733239

RESUMO

BACKGROUND: The salience network (SN) is a transitory mediator between active and passive states of mind. Multiple cortical areas, including the opercular, insular, and cingulate cortices have been linked in this processing, though knowledge of network connectivity has been devoid of structural specificity. OBJECTIVE: The current study sought to create an anatomically specific connectivity model of the neural substrates involved in the salience network. METHODS: A literature search of PubMed and BrainMap Sleuth was conducted for resting-state and task-based fMRI studies relevant to the salience network according to PRISMA guidelines. Publicly available meta-analytic software was utilized to extract relevant fMRI data for the creation of an activation likelihood estimation (ALE) map and relevant parcellations from the human connectome project overlapping with the ALE data were identified for inclusion in our SN model. DSI-based fiber tractography was then performed on publicaly available data from healthy subjects to determine the structural connections between cortical parcellations comprising the network. RESULTS: Nine cortical regions were found to comprise the salience network: areas AVI (anterior ventral insula), MI (middle insula), FOP4 (frontal operculum 4), FOP5 (frontal operculum 5), a24pr (anterior 24 prime), a32pr (anterior 32 prime), p32pr (posterior 32 prime), and SCEF (supplementary and cingulate eye field), and 46. The frontal aslant tract was found to connect the opercular-insular cluster to the middle cingulate clusters of the network, while mostly short U-fibers connected adjacent nodes of the network. CONCLUSION: Here we provide an anatomically specific connectivity model of the neural substrates involved in the salience network. These results may serve as an empiric basis for clinical translation in this region and for future study which seeks to expand our understanding of how specific neural substrates are involved in salience processing and guide subsequent human behavior.


Assuntos
Córtex Cerebral , Conectoma , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Conectoma/métodos , Lobo Frontal , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia
10.
Nat Commun ; 13(1): 3349, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688838

RESUMO

The ability to resolve an approach-avoidance conflict is critical to adaptive behavior. The ventral CA3 (vCA3) and CA1 (vCA1) subfields of the ventral hippocampus (vHPC) have been shown to facilitate avoidance and approach behavior, respectively, in the face of motivational conflict, but the neural circuits by which this subfield-specific regulation is implemented is unknown. We demonstrate that two distinct pathways from these subfields to lateral septum (LS) contribute to this divergent control. In Long-Evans rats, chemogenetic inhibition of the vCA3- LS caudodorsal (cd) pathway potentiated approach towards a learned conflict-eliciting stimulus, while inhibition of the vCA1-LS rostroventral (rv) pathway potentiated approach non-specifically. Additionally, vCA3-LScd inhibited animals were less hesitant to explore food during environmental uncertainty, while the vCA1- LSrv inhibited animals took longer to initiate food exploration. These findings suggest that the vHPC influences multiple behavioral systems via differential projections to the LS, which in turn send inhibitory projections to motivational centres of the brain.


Assuntos
Hipocampo , Inibição Psicológica , Animais , Hipocampo/fisiologia , Vias Neurais/fisiologia , Ratos , Ratos Long-Evans
11.
Neurosci Lett ; 784: 136753, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35753613

RESUMO

INTRODUCTION: There is emerging evidence that high Beta coherence (hBc) between prefrontal and motor corticies, measured with resting-state electroencephalography (rs-EEG), can be an accurate predictor of motor skill learning and stroke recovery. However, it remains unknown whether and how intracortical connectivity may be influenced using neuromodulation. Therefore, a cortico-cortico PAS (ccPAS) paradigm may be used to increase resting-state intracortical connectivity (rs-IC) within a targeted neural circuit. PURPOSE: Our purpose is to demonstrate proof of principle that ccPAS can be used to increase rs-IC between a prefrontal and motor cortical region. METHODS: Eleven non-disabled adults were recruited (mean age 26.4, sd 5.6, 5 female). Each participant underwent a double baseline measurement, followed by a real and control ccPAS condition, counter-balanced for order. Control and ccPAS conditions were performed over electrodes of the right prefrontal and motor cortex. Both ccPAS conditions were identical apart from the inter-stimulus interval (i.e ISI 5 ms: real ccPAS and 500 ms: control ccPAS). Whole brain rs-EEG of high Beta coherence (hBc) was acquired before and after each ccPAS condition and then analyzed for changes in rs-IC along the targeted circuit. RESULTS: Compared to ccPAS500 and baseline, ccPAS5 induced a significant increase in rs-IC, measured as coherence between electrodes over right prefrontal and motor cortex, (p <.05). CONCLUSION: These findings demonstrate proof of principle that ccPAS with an STDP derived ISI, can effectively increase hBc along a targeted circuit.


Assuntos
Córtex Motor , Estimulação Magnética Transcraniana , Adulto , Encéfalo , Eletroencefalografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Córtex Motor/fisiologia , Vias Neurais/fisiologia
12.
Nat Commun ; 13(1): 3623, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35750659

RESUMO

Economic choice requires many cognitive subprocesses, including stimulus detection, valuation, motor output, and outcome monitoring; many of these subprocesses are associated with the central orbitofrontal cortex (cOFC). Prior work has largely assumed that the cOFC is a single region with a single function. Here, we challenge that unified view with convergent anatomical and physiological results from rhesus macaques. Anatomically, we show that the cOFC can be subdivided according to its much stronger (medial) or weaker (lateral) bidirectional anatomical connectivity with the posterior cingulate cortex (PCC). We call these subregions cOFCm and cOFCl, respectively. These two subregions have notable functional differences. Specifically, cOFCm shows enhanced functional connectivity with PCC, as indicated by both spike-field coherence and mutual information. The cOFCm-PCC circuit, but not the cOFCl-PCC circuit, shows signatures of relaying choice signals from a non-spatial comparison framework to a spatially framed organization and shows a putative bidirectional mutually excitatory pattern.


Assuntos
Imageamento por Ressonância Magnética , Córtex Pré-Frontal , Animais , Mapeamento Encefálico , Giro do Cíngulo/fisiologia , Macaca mulatta , Vias Neurais/fisiologia
13.
J Neurosci ; 42(27): 5373-5388, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667849

RESUMO

Pain and emotion are strongly regulated by neurons in the central nucleus of the amygdala (CeA), a major output of the limbic system; yet, the neuronal signaling pathways underlying this modulation are incompletely understood. Here, we characterized a subpopulation of CeA neurons that express the CaMKIIα gene (CeACAM neurons) and project to the lateral parabrachial nucleus (LPBN), a brainstem region known for its critical role in distributing nociceptive and other aversive signals throughout the brain. In male Sprague Dawley rats, we show that CeACAM-LPBN neurons are GABAergic and mostly express somatostatin. In anaesthetized rats, optogenetic stimulation of CeACAM-LPBN projections inhibited responses of LPBN neurons evoked by electrical activation of Aδ- and C-fiber primary afferents; this inhibition could be blocked by intra-LPBN application of the GABAA receptor antagonist bicuculline. CeACAM-LPBN stimulation also dampened LPBN responses to noxious mechanical, thermal, and chemical stimuli. In behaving rats, optogenetic stimulation of CeACAM-LPBN projections attenuated nocifensive responses to mechanical pressure and radiant heat, disrupted the ability of a noxious shock to drive aversive learning, reduced the defensive behaviors of thigmotaxis and freezing, induced place preference, and promoted food consumption in sated rats. Thus, we suggest that CeACAM-LPBN projections mediate a form of analgesia that is accompanied by a shift toward the positive-appetitive pole of the emotional-motivational continuum. Since the affective state of pain patients strongly influences their prognosis, we envision that recruitment of this pathway in a clinical setting could potentially promote pain resilience and recovery.SIGNIFICANCE STATEMENT Pain and emotion interact on multiple levels of the nervous system. Both positive and negative emotion may have analgesic effects. However, while the neuronal mechanisms underlying "stress-induced analgesia" have been the focus of many studies, the neuronal substrates underlying analgesia accompanied by appetitive emotional-motivational states have received far less attention. The current study focuses on a subpopulation of amygdala neurons that form inhibitory synapses within the brainstem lateral parabrachial nucleus (LPBN). We show that activation of these amygdalo-parabrachial projections inhibits pain processing, while also reducing behaviors related to negative affect and enhancing behaviors related to positive affect. We propose that recruitment of this pathway would benefit pain patients, many of whom suffer from psychological comorbidities such as anxiety and depression.


Assuntos
Tonsila do Cerebelo , Núcleos Parabraquiais , Tonsila do Cerebelo/fisiologia , Animais , Emoções , Masculino , Vias Neurais/fisiologia , Dor , Núcleos Parabraquiais/fisiologia , Ratos , Ratos Sprague-Dawley
14.
Proc Natl Acad Sci U S A ; 119(20): e2118712119, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35537049

RESUMO

Alterations in the structure and functional connectivity of anterior thalamic nuclei (ATN) have been linked to reduced cognition during aging. However, ATN circuits that contribute to higher cognitive functions remain understudied. We found that the anteroventral (AV) subdivision of ATN is necessary specifically during the maintenance phase of a spatial working memory task. This function engages the AV→parasubiculum (PaS)→entorhinal cortex (EC) circuit. Aged mice showed a deficit in spatial working memory, which was associated with a decrease in the excitability of AV neurons. Activation of AV neurons or the AV→PaS circuit in aged mice was sufficient to rescue their working memory performance. Furthermore, rescued aged mice showed improved behavior-induced neuronal activity in prefrontal cortex (PFC), a critical site for working memory processes. Although the direct activation of PFC neurons in aged mice also rescued their working memory performance, we found that these animals exhibited increased levels of anxiety, which was not the case for AV→PaS circuit manipulations in aged mice. These results suggest that targeting AV thalamus in aging may not only be beneficial for cognitive functions but that this approach may have fewer unintended effects compared to direct PFC manipulations.


Assuntos
Núcleos Anteriores do Tálamo , Animais , Núcleos Anteriores do Tálamo/fisiologia , Cognição , Transtornos da Memória , Memória de Curto Prazo/fisiologia , Camundongos , Vias Neurais/fisiologia , Neurônios
15.
Cell Rep ; 39(7): 110756, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35584665

RESUMO

How are actions linked with subsequent outcomes to guide choices? The nucleus accumbens, which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex and midline regions of the thalamus. However, little is known about whether and how representations differ across these input pathways. By comparing these inputs during a reinforcement learning task in mice, we discovered that prelimbic cortical inputs preferentially represent actions and choices, whereas midline thalamic inputs preferentially represent cues. Choice-selective activity in the prelimbic cortical inputs is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of reinforcement-learning algorithms, in both a circuit model based on synaptic plasticity and one based on neural dynamics. Finally, we test and confirm a prediction of our circuit models by direct manipulation of nucleus accumbens input neurons.


Assuntos
Núcleo Accumbens , Tálamo , Animais , Camundongos , Vias Neurais/fisiologia , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Reforço Psicológico , Tálamo/fisiologia
16.
Proc Natl Acad Sci U S A ; 119(21): e2201481119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35588455

RESUMO

Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical and subcortical inputs contribute to their distinct output pathways. We used subpopulation specific viral strategies in mice to anatomically and physiologically dissect pathways of the higher-order thalamic nuclei of the somatosensory and visual systems (the posterior medial nucleus and pulvinar). Employing a complementary optogenetics and electrical stimulation strategy, we show that synapses in cortex from higher-order thalamus have functionally divergent properties in primary vs. higher cortical areas. Higher-order thalamic projections onto excitatory targets in S1 and V1 were weakly modulatory, while projections to S2 and higher visual areas were strong drivers of postsynaptic targets. Then, using transsynaptic tracing verified by optogenetics to map inputs to higher-order thalamus, we show that posterior medial nucleus cells projecting to S1 are driven by neurons in layer 5 of S1, S2, and M1 and that pulvinar cells projecting to V1 are driven by neurons in layer 5 of V1 and higher visual areas. Therefore, in both systems, layer 5 of primary and higher cortical areas drives transthalamic feedback modulation of primary sensory cortex through higher-order thalamus. These results highlight conserved organization that may be shared by other thalamocortical circuitry. They also support the hypothesis that direct corticocortical projections in the brain are paralleled by transthalamic pathways, even in the feedback direction, with feedforward transthalamic pathways acting as drivers, while feedback through thalamus is modulatory.


Assuntos
Córtex Somatossensorial , Núcleos Talâmicos , Animais , Camundongos , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico , Córtex Somatossensorial/anatomia & histologia , Córtex Somatossensorial/fisiologia , Sinapses/fisiologia , Núcleos Talâmicos/anatomia & histologia , Núcleos Talâmicos/fisiologia
17.
Nat Neurosci ; 25(6): 714-725, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35590075

RESUMO

Impaired cortical maturation is a postulated mechanism in the etiology of neurodevelopmental disorders, including schizophrenia. In the sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. Whether thalamic activity also shapes prefrontal cortical maturation is unknown. We show that inhibiting the mediodorsal and midline thalamus in mice during adolescence leads to a long-lasting decrease in thalamo-prefrontal projection density and reduced excitatory drive to prefrontal neurons. It also caused prefrontal-dependent cognitive deficits during adulthood associated with disrupted prefrontal cross-correlations and task outcome encoding. Thalamic inhibition during adulthood had no long-lasting consequences. Exciting the thalamus in adulthood during a cognitive task rescued prefrontal cross-correlations, task outcome encoding and cognitive deficits. These data point to adolescence as a sensitive window of thalamocortical circuit maturation. Furthermore, by supporting prefrontal network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders.


Assuntos
Córtex Pré-Frontal , Esquizofrenia , Animais , Inibição Psicológica , Camundongos , Vias Neurais/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Tálamo
18.
Nat Neurosci ; 25(6): 771-782, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35618951

RESUMO

How does the organization of neural information processing enable humans' sophisticated cognition? Here we decompose functional interactions between brain regions into synergistic and redundant components, revealing their distinct information-processing roles. Combining functional and structural neuroimaging with meta-analytic results, we demonstrate that redundant interactions are predominantly associated with structurally coupled, modular sensorimotor processing. Synergistic interactions instead support integrative processes and complex cognition across higher-order brain networks. The human brain leverages synergistic information to a greater extent than nonhuman primates, with high-synergy association cortices exhibiting the highest degree of evolutionary cortical expansion. Synaptic density mapping from positron emission tomography and convergent molecular and metabolic evidence demonstrate that synergistic interactions are supported by receptor diversity and human-accelerated genes underpinning synaptic function. This information-resolved approach provides analytic tools to disentangle information integration from coupling, enabling richer, more accurate interpretations of functional connectivity, and illuminating how the human neurocognitive architecture navigates the trade-off between robustness and integration.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Animais , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Cognição , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/fisiologia , Neuroimagem
19.
Hippocampus ; 32(6): 466-477, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522233

RESUMO

The nucleus reuniens of the thalamus (RE) is an important node between the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Previously, we have shown that its mode of activity and its influence in mPFC-HPC communication is dependent upon brain state. During slow-wave states, RE units are closely and rhythmically coupled to the ongoing mPFC-slow oscillation (SO), while during activated (theta) states, RE neurons fire in an arrhythmic and tonically active manner. Inactivating the RE selectively impoverishes coordination of the SO between mPFC and HPC and interestingly, both mPFC and RE stimulation during the SO cause larger responses in the HPC than during theta. It is unclear if the activity patterns within the RE across states may play a role in both phenomena. Here, we optogenetically excited RE neurons in a tonic fashion to assess the impact on mPFC-HPC coupling. This stimulation decreased the influence of mPFC stimulation in the HPC during SO states, in a manner similar to what is observed across state changes into theta. Importantly, this type of stimulation had no effect on evoked responses during theta. Perhaps more interestingly, tonic optogenetic excitation of the RE also decreased mPFC-HPC SO coherence. Thus, it may not be the integrity of the RE per se that is responsible for efficient communication between mPFC and HPC, but rather the particular state in which RE neurons find themselves. Our results have direct implications for how distant brain regions can communicate most effectively, an issue that is ultimately important for activity-dependent processes occurring during slow-wave sleep-dependent memory consolidation.


Assuntos
Consolidação da Memória , Núcleos da Linha Média do Tálamo , Hipocampo/fisiologia , Consolidação da Memória/fisiologia , Núcleos da Linha Média do Tálamo/fisiologia , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia
20.
Cogn Affect Behav Neurosci ; 22(4): 788-802, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35612724

RESUMO

Previous electroencephalographic and brain stimulation studies have shown that anger responses may be differently lateralized in the prefrontal cortex, with outward-oriented responses (externalized anger) linked to left prefrontal activity, and inward-oriented responses (internalized anger) linked to right prefrontal activity. However, the specific neural structures involved in this asymmetry, and how they interact to produce individual differences, remain unexplored. Furthermore, it is unclear whether such asymmetry may be explained by general behavioral tendencies, known as Behavioral Activation and Behavioral Inhibition Systems (BIS/BAS). Therefore, we analyzed the tendency of externalizing and internalizing anger, respectively measured by the Anger-Out and Anger-In subscales of the State-Trait Anger Expression Inventory, with the patterns of functional connectivity at rest of 71 participants. A left, prefrontal, resting-state, functional connectivity pattern was found for externalizing anger (Anger-Out), including the left inferior frontal gyrus and the left frontal eye fields. By contrast, a right, prefrontal, resting-state, functional connectivity pattern was found for internalizing anger (Anger-In), including the rostral and lateral prefrontal cortex, the orbitofrontal cortex, the frontal pole, the superior, middle and inferior frontal gyri, and the anterior cingulate. Notably, these patterns were not associated with the BIS/BAS scores. In this study, for the first time, we provide evidence using fMRI functional connectivity for two specific lateralized circuits contributing to individual differences in externalizing and internalizing anger. These results confirm and extend the asymmetry hypothesis for anger and have notable implications in the treatment of anger-related problems.


Assuntos
Ira , Imageamento por Ressonância Magnética , Ira/fisiologia , Mapeamento Encefálico , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem
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