RESUMEN
Memories initially formed in hippocampus gradually stabilize to cortex over weeks-to-months for long-term storage. The mechanistic details of this brain re-organization remain poorly understood. We recorded bulk neural activity in circuits that link hippocampus and cortex as mice performed a memory-guided virtual-reality task over weeks. We identified a prominent and sustained neural correlate of memory in anterior thalamus, whose inhibition substantially disrupted memory consolidation. More strikingly, gain amplification enhanced consolidation of otherwise unconsolidated memories. To gain mechanistic insights, we developed a technology for simultaneous cellular-resolution imaging of hippocampus, thalamus, and cortex throughout consolidation. We found that whereas hippocampus equally encodes multiple memories, the anteromedial thalamus preferentially encodes salient memories, and gradually increases correlations with cortex to facilitate tuning and synchronization of cortical ensembles. We thus identify a thalamo-cortical circuit that gates memory consolidation and propose a mechanism suitable for the selection and stabilization of hippocampal memories into longer-term cortical storage.
Asunto(s)
Consolidación de la Memoria , Memoria a Largo Plazo , Ratones , Animales , Memoria a Largo Plazo/fisiología , Tálamo/fisiología , Hipocampo/fisiología , Consolidación de la Memoria/fisiología , EncéfaloRESUMEN
The mystery of general anesthesia is that it specifically suppresses consciousness by disrupting feedback signaling in the brain, even when feedforward signaling and basic neuronal function are left relatively unchanged. The mechanism for such selectiveness is unknown. Here we show that three different anesthetics have the same disruptive influence on signaling along apical dendrites in cortical layer 5 pyramidal neurons in mice. We found that optogenetic depolarization of the distal apical dendrites caused robust spiking at the cell body under awake conditions that was blocked by anesthesia. Moreover, we found that blocking metabotropic glutamate and cholinergic receptors had the same effect on apical dendrite decoupling as anesthesia or inactivation of the higher-order thalamus. If feedback signaling occurs predominantly through apical dendrites, the cellular mechanism we found would explain not only how anesthesia selectively blocks this signaling but also why conscious perception depends on both cortico-cortical and thalamo-cortical connectivity.
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Anestésicos Generales/farmacología , Corteza Cerebral/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Animales , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Antagonistas Colinérgicos/farmacología , Estado de Conciencia , Dendritas/efectos de los fármacos , Dendritas/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Retroalimentación Fisiológica , Femenino , Masculino , Ratones , Células Piramidales/fisiología , Transmisión Sináptica , Tálamo/citología , Tálamo/efectos de los fármacos , Tálamo/fisiologíaRESUMEN
Working memory is a form of short-term memory that involves maintaining and updating task-relevant information toward goal-directed pursuits. Classical models posit persistent activity in prefrontal cortex (PFC) as a primary neural correlate, but emerging views suggest additional mechanisms may exist. We screened â¼200 genetically diverse mice on a working memory task and identified a genetic locus on chromosome 5 that contributes to a substantial proportion (17%) of the phenotypic variance. Within the locus, we identified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory. Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy. These findings identify an orphan receptor as a potent modifier of short-term memory and supplement classical PFC-based models with an emerging thalamus-centric framework for the mechanistic understanding of working memory.
Asunto(s)
Memoria a Corto Plazo/fisiología , Receptores Acoplados a Proteínas G/genética , Tálamo/metabolismo , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Corteza Prefrontal/fisiología , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Flexible behavior requires the creation, updating, and expression of memories to depend on context. While the neural underpinnings of each of these processes have been intensively studied, recent advances in computational modeling revealed a key challenge in context-dependent learning that had been largely ignored previously: Under naturalistic conditions, context is typically uncertain, necessitating contextual inference. We review a theoretical approach to formalizing context-dependent learning in the face of contextual uncertainty and the core computations it requires. We show how this approach begins to organize a large body of disparate experimental observations, from multiple levels of brain organization (including circuits, systems, and behavior) and multiple brain regions (most prominently the prefrontal cortex, the hippocampus, and motor cortices), into a coherent framework. We argue that contextual inference may also be key to understanding continual learning in the brain. This theory-driven perspective places contextual inference as a core component of learning.
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Encéfalo , Aprendizaje , Hipocampo , Corteza Prefrontal , Simulación por ComputadorRESUMEN
Sleep spindles are burstlike signals in the electroencephalogram (EEG) of the sleeping mammalian brain and electrical surface correlates of neuronal oscillations in thalamus. As one of the most inheritable sleep EEG signatures, sleep spindles probably reflect the strength and malleability of thalamocortical circuits that underlie individual cognitive profiles. We review the characteristics, organization, regulation, and origins of sleep spindles and their implication in non-rapid-eye-movement sleep (NREMS) and its functions, focusing on human and rodent. Spatially, sleep spindle-related neuronal activity appears on scales ranging from small thalamic circuits to functional cortical areas, and generates a cortical state favoring intracortical plasticity while limiting cortical output. Temporally, sleep spindles are discrete events, part of a continuous power band, and elements grouped on an infraslow time scale over which NREMS alternates between continuity and fragility. We synthesize diverse and seemingly unlinked functions of sleep spindles for sleep architecture, sensory processing, synaptic plasticity, memory formation, and cognitive abilities into a unifying sleep spindle concept, according to which sleep spindles 1) generate neural conditions of large-scale functional connectivity and plasticity that outlast their appearance as discrete EEG events, 2) appear preferentially in thalamic circuits engaged in learning and attention-based experience during wakefulness, and 3) enable a selective reactivation and routing of wake-instated neuronal traces between brain areas such as hippocampus and cortex. Their fine spatiotemporal organization reflects NREMS as a physiological state coordinated over brain and body and may indicate, if not anticipate and ultimately differentiate, pathologies in sleep and neurodevelopmental, -degenerative, and -psychiatric conditions.
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Ondas Encefálicas , Encéfalo/fisiopatología , Cognición , Enfermedades del Sistema Nervioso/fisiopatología , Periodicidad , Fases del Sueño , Trastornos del Sueño-Vigilia/fisiopatología , Animales , Atención , Encéfalo/metabolismo , Humanos , Inteligencia , Memoria , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/psicología , Plasticidad Neuronal , Trastornos del Sueño-Vigilia/genética , Trastornos del Sueño-Vigilia/metabolismo , Trastornos del Sueño-Vigilia/psicología , Factores de TiempoRESUMEN
Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing next generation therapeutics to treat absence epilepsy.
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Modelos Animales de Enfermedad , Epilepsia Tipo Ausencia , Animales , Epilepsia Tipo Ausencia/fisiopatología , Ratones , Tálamo/fisiopatología , Neuronas/metabolismo , Neuronas/fisiología , Optogenética , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Estimulación Encefálica Profunda/métodos , Masculino , Núcleos Talámicos de la Línea Media/fisiologíaRESUMEN
Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.
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Estimulación Encefálica Profunda , Núcleo Subtalámico , Animales , Humanos , Tálamo/fisiología , Neuronas/fisiología , MicroelectrodosRESUMEN
The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first-time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2+ /Galanin+ neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC-CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first-time exposure to pups.
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Conducta Materna , Periodo Posparto , Humanos , Animales , Ratones , Femenino , Periodo Posparto/fisiología , Neuronas/fisiología , Tálamo , Corteza Prefrontal , Conducta AnimalRESUMEN
The thalamus has long been suspected to have an important role in cognition, yet recent theories have favored a more corticocentric view. According to this view, the thalamus is an excitatory feedforward relay to or between cortical regions, and cognitively relevant computations are exclusively cortical. Here, we review anatomical, physiological, and behavioral studies along evolutionary and theoretical dimensions, arguing for essential and unique thalamic computations in cognition. Considering their architectural features as well as their ability to initiate, sustain, and switch cortical activity, thalamic circuits appear uniquely suited for computing contextual signals that rapidly reconfigure task-relevant cortical representations. We introduce a framework that formalizes this notion, show its consistency with several findings, and discuss its prediction of thalamic roles in perceptual inference and behavioral flexibility. Overall, our framework emphasizes an expanded view of the thalamus in cognitive computations and provides a roadmap to test several of its theoretical and experimental predictions.
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Corteza Cerebral/fisiología , Cognición/fisiología , Modelos Neurológicos , Vías Nerviosas/fisiología , Tálamo/fisiología , Animales , Corteza Cerebral/anatomía & histología , Simulación por Computador , Humanos , Vías Nerviosas/anatomía & histología , Tálamo/anatomía & histologíaRESUMEN
Neural proliferation zones mediate brain growth and employ Delta/Notch signaling and HES/Her transcription factors to balance neural stem cell (NSC) maintenance with the generation of progenitors and neurons. We investigated Notch-dependency and function of her genes in the thalamic proliferation zone of zebrafish larvae. Nine Notch-dependent genes, her2, her4.1-4.5, her12, her15.1-15.2, and two Notch-independent genes, her6 and her9, are differentially expressed and define distinct NSC and progenitor populations. her6 prominently executes patterning information to maintain NSCs and the zona limitans intrathalamica Shh signaling activity. Surprisingly, simultaneous deletion of nine Notch-dependent her genes does not affect NSCs or progenitor formation, and her4 overexpression only caused reduction of ascl1b progenitors. Combined genetic manipulations of Notch-dependent and -independent her genes suggest that her6 in the thalamic proliferation zone prominently maintains NSCs and inhibits NSC-to-progenitor lineage transitions. The her gene network is characterized by redundant gene functions, with Notch-independent her genes better substituting for loss of Notch-dependent her genes than vice versa. Together, her gene regulatory feedback loops and cross-regulation contribute to the observed robustness of NSC maintenance.
Asunto(s)
Proliferación Celular , Regulación del Desarrollo de la Expresión Génica , Células Madre , Pez Cebra , Receptores Notch/genética , Receptores Notch/metabolismo , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Células Madre/citología , Células Madre/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Familia de Multigenes , AnimalesRESUMEN
Understanding the neurobiological mechanisms underlying consciousness remains a significant challenge. Recent evidence suggests that the coupling between distal-apical and basal-somatic dendrites in thick-tufted layer 5 pyramidal neurons (L5PN), regulated by the nonspecific-projecting thalamus, is crucial for consciousness. Yet, it is uncertain whether this thalamocortical mechanism can support emergent signatures of consciousness, such as integrated information. To address this question, we constructed a biophysical network of dual-compartment thick-tufted L5PN, with dendrosomatic coupling controlled by thalamic inputs. Our findings demonstrate that integrated information is maximized when nonspecific thalamic inputs drive the system into a regime of time-varying synchronous bursting. Here, the system exhibits variable spiking dynamics with broad pairwise correlations, supporting the enhanced integrated information. Further, the observed peak in integrated information aligns with criticality signatures and empirically observed layer 5 pyramidal bursting rates. These results suggest that the thalamocortical core of the mammalian brain may be evolutionarily configured to optimize effective information processing, providing a potential neuronal mechanism that integrates microscale theories with macroscale signatures of consciousness.
Asunto(s)
Neuronas , Células Piramidales , Animales , Neuronas/fisiología , Células Piramidales/fisiología , Dendritas/fisiología , Tálamo/fisiología , MamíferosRESUMEN
Chronic opioid exposure induces tolerance to the pain-relieving effects of opioids but sensitization to some other effects. While the occurrence of these adaptations is well understood, the underlying cellular mechanisms are less clear. This study aimed to determine how chronic treatment with morphine, a prototypical opioid agonist, induced adaptations to subsequent morphine signaling in different subcellular contexts. Opioids acutely inhibit glutamatergic transmission from medial thalamic (MThal) inputs to the dorsomedial striatum (DMS) via activity at µ-opioid receptors (MORs). MORs are present in somatic and presynaptic compartments of MThal neurons terminating in the DMS. We investigated the effects of chronic morphine treatment on subsequent morphine signaling at MThal-DMS synapses and MThal cell bodies in male and female mice. Surprisingly, chronic morphine treatment increased subsequent morphine inhibition of MThal-DMS synaptic transmission (morphine facilitation) in male, but not female, mice. At MThal cell bodies, chronic morphine treatment decreased subsequent morphine activation of potassium conductance (morphine tolerance) in both male and female mice. In knock-in mice expressing phosphorylation-deficient MORs, chronic morphine treatment resulted in tolerance to, rather than facilitation of, subsequent morphine signaling at MThal-DMS terminals, suggesting phosphorylation deficiency unmasks adaptations that counter the facilitation observed at presynaptic terminals in wild-type mice. The results of this study suggest that the effects of chronic morphine exposure are not ubiquitous; rather adaptations in MOR function may be determined by multiple factors such as subcellular receptor distribution, influence of local circuitry, and sex.
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Analgésicos Opioides , Morfina , Masculino , Femenino , Ratones , Animales , Morfina/farmacología , Analgésicos Opioides/farmacología , Fosforilación , Transducción de Señal , Receptores Opioides , Receptores Opioides mu/agonistasRESUMEN
In 1998, Jones suggested a classification of thalamocortical projections into core and matrix divisions (Jones, 1998). In this classification, core projections are specific, topographical, innervate middle cortical layers, and serve to transmit specific information to the cortex for further analysis; matrix projections, in contrast, are diffuse, much less topographic, innervate upper layers, especially Layer 1, and serve a more global, modulatory function, such as affecting levels of arousal. This classification has proven especially influential in studies of thalamocortical relationships. Whereas it may be the case that a clear subset of thalamocortical connections fit the core motif, since they are specific, topographic, and innervate middle layers, we argue that there is no clear evidence for any single class that encompasses the remainder of thalamocortical connections as is claimed for matrix. Instead, there is great morphological variation in connections made by thalamocortical projections fitting neither a core nor matrix classification. We thus conclude that the core/matrix classification should be abandoned, because its application is not helpful in providing insights into thalamocortical interactions and can even be misleading. As one example of the latter, recent suggestions indicate that core projections are equivalent to first-order thalamic relays (i.e., those that relay subcortical information to the cortex) and matrix to higher-order relays (i.e., those that relay information from one cortical area to another), but available evidence does not support this relationship. All of this points to a need to replace the core/matrix grouping with a more complete classification of thalamocortical projections.
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Corteza Cerebral , Vías Nerviosas , Tálamo , Tálamo/fisiología , Tálamo/anatomía & histología , Corteza Cerebral/fisiología , Corteza Cerebral/anatomía & histología , Humanos , Animales , Vías Nerviosas/fisiología , Vías Nerviosas/anatomía & histologíaRESUMEN
The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways and the difference increases with luminance range (defined as the maximum minus minimum luminance in the scene). Here, we demonstrate that these ON-OFF cortical differences are already present in the human retina and that retinal responses measured with electroretinography are more affected by reductions in luminance range than cortical responses measured with electroencephalography. Moreover, we show that ON-OFF pathway differences measured with electroretinography become more pronounced in myopia, a visual disorder that elongates the eye and blurs vision at far distance. We find that, as the eye axial length increases across subjects, ON retinal pathways become less responsive, slower in response latency, less sensitive, and less effective and slower at driving pupil constriction. Based on these results, we conclude that myopia is associated with a deficit in ON pathway function that decreases the ability of the retina to process low contrast and regulate retinal illuminance in bright environments.
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Sensibilidad de Contraste , Miopía , Humanos , Retina/fisiología , Visión Ocular , Electrorretinografía , Estimulación LuminosaRESUMEN
Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain.
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Estimulación Acústica , Cuerpos Geniculados , Neuronas , Ratas Sprague-Dawley , Animales , Femenino , Ratas , Neuronas/fisiología , Cuerpos Geniculados/fisiología , Estimulación Acústica/métodos , Vías Auditivas/fisiología , Potenciales de Acción/fisiología , Corteza Auditiva/fisiología , Corteza Auditiva/citología , Tálamo/fisiología , Tálamo/citología , Potenciales Evocados Auditivos/fisiologíaRESUMEN
Interneurons in the medial prefrontal cortex (PFC) regulate local neural activity to influence cognitive, motivated, and emotional behaviors. Parvalbumin-expressing (PV+) interneurons are the primary mediators of thalamus-evoked feed-forward inhibition across the mouse cortex, including the anterior cingulate cortex, where they are engaged by inputs from the mediodorsal (MD) thalamus. In contrast, in the adjacent prelimbic (PL) cortex, we find that PV+ interneurons are scarce in the principal thalamorecipient layer 3 (L3), suggesting distinct mechanisms of inhibition. To identify the interneurons that mediate MD-evoked inhibition in PL, we combine slice physiology, optogenetics, and intersectional genetic tools in mice of both sexes. We find interneurons expressing cholecystokinin (CCK+) are abundant in L3 of PL, with cells exhibiting fast-spiking (fs) or non-fast-spiking (nfs) properties. MD inputs make stronger connections onto fs-CCK+ interneurons, driving them to fire more readily than nearby L3 pyramidal cells and other interneurons. CCK+ interneurons in turn make inhibitory, perisomatic connections onto L3 pyramidal cells, where they exhibit cannabinoid 1 receptor (CB1R) mediated modulation. Moreover, MD-evoked feed-forward inhibition, but not direct excitation, is also sensitive to CB1R modulation. Our findings indicate that CCK+ interneurons contribute to MD-evoked inhibition in PL, revealing a mechanism by which cannabinoids can modulate MD-PFC communication.
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Colecistoquinina , Interneuronas , Inhibición Neural , Corteza Prefrontal , Animales , Interneuronas/fisiología , Colecistoquinina/metabolismo , Corteza Prefrontal/fisiología , Ratones , Masculino , Femenino , Inhibición Neural/fisiología , Tálamo/fisiología , Ratones Endogámicos C57BL , Parvalbúminas/metabolismo , Ratones Transgénicos , Vías Nerviosas/fisiología , OptogenéticaRESUMEN
Navigating a complex world requires integration of multiple spatial reference frames, including information about one's orientation in both allocentric and egocentric coordinates. Combining these two information sources can provide additional information about one's spatial location. Previous studies have demonstrated that both egocentric and allocentric spatial signals are reflected by the firing of neurons in the rat postrhinal cortex (POR), an area that may serve as a hub for integrating allocentric head direction (HD) cell information with egocentric information from center-bearing and center-distance cells. However, we have also demonstrated that POR HD cells are uniquely influenced by the visual properties and locations of visual landmarks, bringing into question whether the POR HD signal is truly allocentric as opposed to simply being a response to visual stimuli. To investigate this issue, we recorded HD cells from the POR of female rats while bilaterally inactivating the anterior thalamus (ATN), a region critical for expression of the "classic" HD signal in cortical areas. We found that ATN inactivation led to a significant decrease in both firing rate and tuning strength for POR HD cells, as well as a disruption in the encoding of allocentric location by conjunctive HD/egocentric cells. In contrast, POR egocentric cells without HD tuning were largely unaffected in a consistent manner by ATN inactivation. These results indicate that the POR HD signal originates at least partially from projections from the ATN and supports the view that the POR acts as a hub for the integration of egocentric and allocentric spatial representations.
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Núcleos Talámicos Anteriores , Ratas , Femenino , Animales , Orientación/fisiología , Percepción Espacial/fisiologíaRESUMEN
The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain's tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.
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Colículos Inferiores , Parvalbúminas , Femenino , Masculino , Ratones , Animales , Parvalbúminas/metabolismo , Colículos Inferiores/fisiología , Neuronas/fisiología , Vías Auditivas/fisiología , Somatostatina/metabolismoRESUMEN
Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials (Vm ) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a Gi/o -coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a subset of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of Vm Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and Vm dynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold Vm dynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons in wS1, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1.
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Neuronas , Corteza Somatosensorial , Ratones , Masculino , Animales , Neuronas/fisiología , Corteza Somatosensorial/fisiología , Axones , Potenciales de la Membrana , Movimiento , Vibrisas/fisiologíaRESUMEN
The key assumption of the predictive coding framework is that internal representations are used to generate predictions on how the sensory input will look like in the immediate future. These predictions are tested against the actual input by the so-called prediction error units, which encode the residuals of the predictions. What happens to prediction errors, however, if predictions drawn by different stages of the sensory hierarchy contradict each other? To answer this question, we conducted two fMRI experiments while female and male human participants listened to sequences of sounds: pure tones in the first experiment and frequency-modulated sweeps in the second experiment. In both experiments, we used repetition to induce predictions based on stimulus statistics (stats-informed predictions) and abstract rules disclosed in the task instructions to induce an orthogonal set of (task-informed) predictions. We tested three alternative scenarios: neural responses in the auditory sensory pathway encode prediction error with respect to (1) the stats-informed predictions, (2) the task-informed predictions, or (3) a combination of both. Results showed that neural populations in all recorded regions (bilateral inferior colliculus, medial geniculate body, and primary and secondary auditory cortices) encode prediction error with respect to a combination of the two orthogonal sets of predictions. The findings suggest that predictive coding exploits the non-linear architecture of the auditory pathway for the transmission of predictions. Such non-linear transmission of predictions might be crucial for the predictive coding of complex auditory signals like speech.Significance Statement Sensory systems exploit our subjective expectations to make sense of an overwhelming influx of sensory signals. It is still unclear how expectations at each stage of the processing pipeline are used to predict the representations at the other stages. The current view is that this transmission is hierarchical and linear. Here we measured fMRI responses in auditory cortex, sensory thalamus, and midbrain while we induced two sets of mutually inconsistent expectations on the sensory input, each putatively encoded at a different stage. We show that responses at all stages are concurrently shaped by both sets of expectations. The results challenge the hypothesis that expectations are transmitted linearly and provide for a normative explanation of the non-linear physiology of the corticofugal sensory system.