ABSTRACT
New tasks are often learned in stages with each stage reflecting a different learning challenge. Accordingly, each learning stage is likely mediated by distinct neuronal processes. And yet, most rodent studies of the neuronal correlates of goal-directed learning focus on individual outcome measures and individual brain regions. Here, we longitudinally studied mice from naïve to expert performance in a head-fixed, operant conditioning whisker discrimination task. In addition to tracking the primary behavioral outcome of stimulus discrimination, we tracked and compared an array of object-based and temporal-based behavioral measures. These behavioral analyses identify multiple, partially overlapping learning stages in this task, consistent with initial response implementation, early stimulus-response generalization, and late response inhibition. To begin to understand the neuronal foundations of these learning processes, we performed widefield Ca2+ imaging of dorsal neocortex throughout learning and correlated behavioral measures with neuronal activity. We found distinct and widespread correlations between neocortical activation patterns and various behavioral measures. For example, improvements in sensory discrimination correlated with target stimulus evoked activations of response-related cortices along with distractor stimulus evoked global cortical suppression. Our study reveals multidimensional learning for a simple goal-directed learning task and generates hypotheses for the neuronal modulations underlying these various learning processes.
Subject(s)
Conditioning, Operant , Goals , Neocortex , Vibrissae , Animals , Neocortex/physiology , Conditioning, Operant/physiology , Vibrissae/physiology , Male , Mice , Mice, Inbred C57BL , Female , Discrimination Learning/physiology , Learning/physiology , Neurons/physiologyABSTRACT
The role of developmental cell death in the formation of brain circuits is not well understood. Cajal-Retzius cells constitute a major transient neuronal population in the mammalian neocortex, which largely disappears at the time of postnatal somatosensory maturation. In this study, we used mouse genetics, anatomical, functional, and behavioral approaches to explore the impact of the early postnatal death of Cajal-Retzius cells in the maturation of the cortical circuit. We find that before their death, Cajal-Retzius cells mainly receive inputs from layer 1 neurons, which can only develop their mature connectivity onto layer 2/3 pyramidal cells after Cajal-Retzius cells disappear. This developmental connectivity progression from layer 1 GABAergic to layer 2/3 pyramidal cells regulates sensory-driven inhibition within, and more so, across cortical columns. Here we show that Cajal-Retzius cell death prevention leads to layer 2/3 hyper-excitability, delayed learning and reduced performance in a multi-whisker-dependent texture discrimination task.
Subject(s)
Cell Death , Pyramidal Cells , Somatosensory Cortex , Animals , Somatosensory Cortex/physiology , Somatosensory Cortex/cytology , Mice , Pyramidal Cells/physiology , Pyramidal Cells/metabolism , Neocortex/cytology , Neocortex/physiology , GABAergic Neurons/physiology , GABAergic Neurons/metabolism , Male , Vibrissae/physiology , Female , Mice, Inbred C57BL , Neural Inhibition/physiology , Neurons/physiology , Neurons/metabolismABSTRACT
Goal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.
Subject(s)
Memory, Short-Term , Perirhinal Cortex , Animals , Mice , Perirhinal Cortex/physiology , Memory, Short-Term/physiology , Male , Learning/physiology , Mice, Inbred C57BL , Vibrissae/physiology , Acetylcholine/metabolism , Behavior, Animal/physiology , FemaleABSTRACT
Rodents continuously move their heads and whiskers in a coordinated manner while perceiving objects through whisker-touch. Studies in head-fixed rodents showed that the ventroposterior medial (VPM) and posterior medial (POm) thalamic nuclei code for whisker kinematics, with POm involvement reduced in awake animals. To examine VPM and POm involvement in coding head and whisker kinematics in awake, head-free conditions, we recorded thalamic neuronal activity and tracked head and whisker movements in male mice exploring an open arena. Using optogenetic tagging, we found that in freely moving mice, both nuclei equally coded whisker kinematics and robustly coded head kinematics. The fraction of neurons coding head kinematics increased after whisker trimming, ruling out whisker-mediated coding. Optogenetic activation of thalamic neurons evoked overt kinematic changes and increased the fraction of neurons leading changes in head kinematics. Our data suggest that VPM and POm integrate head and whisker information and can influence head kinematics during tactile perception.
Subject(s)
Neurons , Optogenetics , Vibrissae , Animals , Vibrissae/physiology , Male , Neurons/physiology , Mice , Biomechanical Phenomena , Head Movements/physiology , Head/physiology , Mice, Inbred C57BL , Touch Perception/physiology , Thalamus/physiology , Thalamus/cytologyABSTRACT
Synaptic potentiation has been linked to learning in sensory cortex, but the connection between this potentiation and increased sensory-evoked neural activity is not clear. Here, we used longitudinal in vivo Ca2+ imaging in the barrel cortex of awake mice to test the hypothesis that increased excitatory synaptic strength during the learning of a whisker-dependent sensory-association task would be correlated with enhanced stimulus-evoked firing. To isolate stimulus-evoked responses from dynamic, task-related activity, imaging was performed outside of the training context. Although prior studies indicate that multiwhisker stimuli drive robust subthreshold activity, we observed sparse activation of L2/3 pyramidal (Pyr) neurons in both control and trained mice. Despite evidence for excitatory synaptic strengthening at thalamocortical and intracortical synapses in this brain area at the onset of learning-indeed, under our imaging conditions thalamocortical axons were robustly activated-we observed that L2/3 Pyr neurons in somatosensory (barrel) cortex displayed only modest increases in stimulus-evoked activity that were concentrated at the onset of training. Activity renormalized over longer training periods. In contrast, when stimuli and rewards were uncoupled in a pseudotraining paradigm, stimulus-evoked activity in L2/3 Pyr neurons was significantly suppressed. These findings indicate that sensory-association training but not sensory stimulation without coupled rewards may briefly enhance sensory-evoked activity, a phenomenon that might help link sensory input to behavioral outcomes at the onset of learning.
Subject(s)
Neocortex , Somatosensory Cortex , Vibrissae , Animals , Vibrissae/physiology , Neocortex/physiology , Mice , Somatosensory Cortex/physiology , Male , Pyramidal Cells/physiology , Mice, Inbred C57BL , Female , Association Learning/physiologyABSTRACT
OBJECTIVE: Childhood sensory abnormalities experience has a crucial influence on the structure and function of the adult brain. The underlying mechanism of neurological function induced by childhood sensory abnormalities experience is still unclear. Our study was to investigate whether the GABAergic neurons in the anterior cingulate cortex (ACC) regulate social disorders caused by childhood sensory abnormalities experience. METHODS: We used two mouse models, complete Freund's adjuvant (CFA) injection mice and bilateral whisker trimming (BWT) mice in childhood. We applied immunofluorescence, chemogenetic and optogenetic to study the mechanism of parvalbumin (PV) neurons and somatostatin (SST) neurons in ACC in regulating social disorders induced by sensory abnormalities in childhood. RESULTS: Inflammatory pain in childhood leads to social preference disorders, while BWT in childhood leads to social novelty disorders in adult mice. Inflammatory pain and BWT in childhood caused an increase in the number of PV and SST neurons, respectively, in adult mice ACC. Inhibiting PV neurons in ACC improved social preference disorders in adult mice that experienced inflammatory pain during childhood. Inhibiting SST neurons in ACC improved social novelty disorders in adult mice that experienced BWT in childhood. CONCLUSIONS: Our study reveals that PV and SST neurons of the ACC may play a critical role in regulating social disorders induced by sensory abnormalities in childhood.
Subject(s)
Gyrus Cinguli , Mice, Inbred C57BL , Parvalbumins , Somatostatin , Animals , Mice , Somatostatin/metabolism , Male , Parvalbumins/metabolism , GABAergic Neurons/physiology , Freund's Adjuvant/toxicity , Vibrissae/physiology , Vibrissae/innervation , Neurons , Social Behavior Disorders/etiology , Mice, TransgenicABSTRACT
Sensory adaptation is the process whereby brain circuits adjust neuronal activity in response to redundant sensory stimuli. Although sensory adaptation has been extensively studied for individual neurons on timescales of tens of milliseconds to a few seconds, little is known about it over longer timescales or at the population level. We investigated population-level adaptation in the barrel field of the mouse somatosensory cortex (S1BF) using in vivo two-photon calcium imaging and Neuropixels recordings in awake mice. Among stimulus-responsive neurons, we found both adapting and facilitating neurons, which decreased or increased their firing, respectively, with repetitive whisker stimulation. The former outnumbered the latter by 2:1 in layers 2/3 and 4; hence, the overall population response of mouse S1BF was slightly adapting. We also discovered that population adaptation to one stimulus frequency (5 Hz) does not necessarily generalize to a different frequency (12.5 Hz). Moreover, responses of individual neurons to repeated rounds of stimulation over tens of minutes were strikingly heterogeneous and stochastic, such that their adapting or facilitating response profiles were not stable across time. Such representational drift was particularly striking when recording longitudinally across 8-9 days, as adaptation profiles of most whisker-responsive neurons changed drastically from one day to the next. Remarkably, repeated exposure to a familiar stimulus paradoxically shifted the population away from strong adaptation and toward facilitation. Thus, the adapting vs. facilitating response profile of S1BF neurons is not a fixed property of neurons but rather a highly dynamic feature that is shaped by sensory experience across days.
Subject(s)
Adaptation, Physiological , Somatosensory Cortex , Vibrissae , Animals , Somatosensory Cortex/physiology , Mice , Vibrissae/physiology , Adaptation, Physiological/physiology , Male , Neurons/physiology , Mice, Inbred C57BL , Female , Physical StimulationABSTRACT
During learning of a sensory discrimination task, the cortical and subcortical regions display complex spatiotemporal dynamics. During learning, both the amygdala and cortex link stimulus information to its appropriate association, for example, a reward. In addition, both structures are also related to nonsensory parameters such as body movements and licking during the reward period. However, the emergence of the cortico-amygdala relationships during learning is largely unknown. To study this, we combined wide-field cortical imaging with fiber photometry to simultaneously record cortico-amygdala population dynamics as male mice learn a whisker-dependent go/no-go task. We were able to simultaneously record neuronal populations from the posterior cortex and either the basolateral amygdala (BLA) or central/medial amygdala (CEM). Prior to learning, the somatosensory and associative cortex responded during sensation, while amygdala areas did not show significant responses. As mice became experts, amygdala responses emerged early during the sensation period, increasing in the CEM, while decreasing in the BLA. Interestingly, amygdala and cortical responses were associated with task-related body movement, displaying significant responses â¼200â ms before movement initiation which led to licking for the reward. A correlation analysis between the cortex and amygdala revealed negative and positive correlation with the BLA and CEM, respectively, only in the expert case. These results imply that learning induces an involvement of the cortex and amygdala which may aid to link sensory stimuli with appropriate associations.
Subject(s)
Amygdala , Mice, Inbred C57BL , Animals , Male , Amygdala/physiology , Mice , Cerebral Cortex/physiology , Vibrissae/physiology , Vibrissae/innervation , Discrimination Learning/physiology , Discrimination, Psychological/physiology , Reward , Learning/physiologyABSTRACT
Rodents use their whisker system to discriminate surface texture. Whisker-based texture discrimination tasks are often used to investigate the mechanisms encoding tactile sensation. One such task is the textured Novel Object Recognition Test (tNORT). It takes advantage of a tendency of rodents to explore novel objects more than familiar ones and assesses the sensitivity of whiskers in discriminating different textures of objects. It requires little training of the animals and the equipment involved is a simple arena with typically two objects placed inside. The success of the test relies on rodents spending sufficient time exploring these objects. Animals may lose interests in such tasks when performed repetitively within a limited time frame. However, such repeated tests may be crucial when establishing a sensitivity threshold of the whisker system. Here we present an adapted rodent tNORT protocol designed to maintain sustained interest in the objects even with repeated testing. We constructed complex objects from three simple-shaped objects. Different textures were provided by sandpapers of varying grit sizes. To minimise olfactory clues, we used the sandy and the laminar side of the same sandpaper as the familiar and novel textures assigned at random. We subsequently conducted repeated tNORTs on eight rats in order to identify a critical threshold of the sandpaper grit size below which rats would be unable to discriminate the sandy from the laminar side. With an inter-test-interval of seven days and after five tNORTs, the protocol enabled us to successfully identify the threshold. We suggest that the proposed tNORT is a useful tool for investigating the sensitivity threshold of the whisker system of rodent, and for testing the effectiveness of an intervention by comparing sensitivity threshold pre- and post-intervention.
Subject(s)
Recognition, Psychology , Touch Perception , Vibrissae , Animals , Vibrissae/physiology , Recognition, Psychology/physiology , Rats , Touch Perception/physiology , Male , Exploratory Behavior/physiology , Discrimination, Psychological/physiology , Touch/physiology , Sensory Thresholds/physiologyABSTRACT
Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors ß-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/ß-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing.
Subject(s)
Cell Proliferation , Exosomes , Fibroblasts , Hair Follicle , Mice, Nude , Regeneration , Vibrissae , Wnt Signaling Pathway , Wound Healing , beta Catenin , Animals , Mice , Fibroblasts/metabolism , Exosomes/metabolism , Vibrissae/physiology , beta Catenin/metabolism , Dermis/metabolism , Cell Movement , Lymphoid Enhancer-Binding Factor 1/metabolismABSTRACT
For neural circuit construction in the brain, coarse neuronal connections are assembled prenatally following genetic programs, being reorganized postnatally by activity-dependent mechanisms to implement area-specific computational functions. Activity-dependent dendrite patterning is a critical component of neural circuit reorganization, whereby individual neurons rearrange and optimize their presynaptic partners. In the rodent primary somatosensory cortex (barrel cortex), driven by thalamocortical inputs, layer 4 (L4) excitatory neurons extensively remodel their basal dendrites at neonatal stages to ensure specific responses of barrels to the corresponding individual whiskers. This feature of barrel cortex L4 neurons makes them an excellent model, significantly contributing to unveiling the activity-dependent nature of dendrite patterning and circuit reorganization. In this review, we summarize recent advances in our understanding of the activity-dependent mechanisms underlying dendrite patterning. Our focus lays on the mechanisms revealed by in vivo time-lapse imaging, and the role of activity-dependent Golgi apparatus polarity regulation in dendrite patterning. We also discuss the type of neuronal activity that could contribute to dendrite patterning and hence connectivity.
Subject(s)
Dendrites , Somatosensory Cortex , Vibrissae , Animals , Dendrites/physiology , Somatosensory Cortex/physiology , Somatosensory Cortex/growth & development , Somatosensory Cortex/cytology , Vibrissae/physiology , Animals, NewbornABSTRACT
During perceptually guided decisions, correlates of choice are found as upstream as in the primary sensory areas. However, how well these choice signals align with early sensory representations, a prerequisite for their interpretation as feedforward substrates of perception, remains an open question. We designed a two alternative forced choice task (2AFC) in which male mice compared stimulation frequencies applied to two adjacent vibrissae. The optogenetic silencing of individual columns in the primary somatosensory cortex (wS1) resulted in predicted shifts of psychometric functions, demonstrating that perception depends on focal, early sensory representations. Functional imaging of layer II/III single neurons revealed mixed coding of stimuli, choices and engagement in the task. Neurons with multi-whisker suppression display improved sensory discrimination and had their activity increased during engagement in the task, enhancing selectively representation of the signals relevant to solving the task. From trial to trial, representation of stimuli and choice varied substantially, but mostly orthogonally to each other, suggesting that perceptual variability does not originate from wS1 fluctuations but rather from downstream areas. Together, our results highlight the role of primary sensory areas in forming a reliable sensory substrate that could be used for flexible downstream decision processes.
Subject(s)
Choice Behavior , Optogenetics , Somatosensory Cortex , Vibrissae , Animals , Somatosensory Cortex/physiology , Male , Vibrissae/physiology , Choice Behavior/physiology , Mice , Neurons/physiology , Mice, Inbred C57BLABSTRACT
Dopamine critically influences reward processing, sensory perception, and motor control. Yet, the modulation of dopaminergic signaling by sensory experiences is not fully delineated. Here, by manipulating sensory experience using bilateral single-row whisker deprivation, we demonstrated that gene transcription in the dopaminergic signaling pathway (DSP) undergoes experience-dependent plasticity in both granular and supragranular layers of the primary somatosensory (barrel) cortex (S1). Sensory experience and deprivation compete for the regulation of DSP transcription across neighboring cortical columns, and sensory deprivation-induced changes in DSP are topographically constrained. These changes in DSP extend beyond cortical map plasticity and influence neuronal information processing. Pharmacological regulation of D2 receptors, a key component of DSP, revealed that D2 receptor activation suppresses excitatory neuronal excitability, hyperpolarizes the action potential threshold, and reduces the instantaneous firing rate. These findings suggest that the dopaminergic drive originating from midbrain dopaminergic neurons, targeting the sensory cortex, is subject to experience-dependent regulation and might create a regulatory feedback loop for modulating sensory processing. Finally, using topological gene network analysis and mutual information, we identify the molecular hubs of experience-dependent plasticity of DSP. These findings provide new insights into the mechanisms by which sensory experience shapes dopaminergic signaling in the brain and might help unravel the sensory deficits observed after dopamine depletion.
Subject(s)
Dopamine , Neuronal Plasticity , Signal Transduction , Somatosensory Cortex , Somatosensory Cortex/metabolism , Somatosensory Cortex/physiology , Animals , Signal Transduction/physiology , Dopamine/metabolism , Neuronal Plasticity/physiology , Dopaminergic Neurons/physiology , Dopaminergic Neurons/metabolism , Vibrissae/physiology , Receptors, Dopamine D2/metabolism , Sensory Deprivation/physiology , Mice , MaleABSTRACT
In the rodent whisker system, active sensing and sensorimotor integration are mediated in part by the dynamic interactions between the motor cortex (M1) and somatosensory cortex (S1). However, understanding these dynamic interactions requires knowledge about the synapses and how specific neurons respond to their input. Here, we combined optogenetics, retrograde labeling, and electrophysiology to characterize the synaptic connections between M1 and layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons in S1 of mice (both sexes). We found that M1 synapses onto IT cells displayed modest short-term depression, whereas synapses onto PT neurons showed robust short-term facilitation. Despite M1 inputs to IT cells depressing, their slower kinetics resulted in summation and a response that increased during short trains. In contrast, summation was minimal in PT neurons due to the fast time course of their M1 responses. The functional consequences of this reduced summation, however, were outweighed by the strong facilitation at these M1 synapses, resulting in larger response amplitudes in PT neurons than IT cells during repetitive stimulation. To understand the impact of facilitating M1 inputs on PT output, we paired trains of inputs with single backpropagating action potentials, finding that repetitive M1 activation increased the probability of bursts in PT cells without impacting the time dependence of this coupling. Thus, there are two parallel but dynamically distinct systems of M1 synaptic excitation in L5 of S1, each defined by the short-term dynamics of its synapses, the class of postsynaptic neurons, and how the neurons respond to those inputs.
Subject(s)
Motor Cortex , Optogenetics , Somatosensory Cortex , Animals , Somatosensory Cortex/physiology , Motor Cortex/physiology , Male , Female , Neural Pathways/physiology , Synapses/physiology , Mice , Neurons/physiology , Mice, Inbred C57BL , Vibrissae/physiology , Pyramidal Tracts/physiology , Mice, Transgenic , Excitatory Postsynaptic Potentials/physiologyABSTRACT
OBJECTIVE: Chronic constriction injury (CCI) of the infraorbital nerve induces neuropathic pain, such as allodynia and hyperalgesia, in the orofacial area. However, the changes in the local circuits of the central nervous system following CCI remain unclear. This study aimed to identify the changes following CCI in Thy1-GCaMP6s transgenic mice. METHODS: Neural activity in the primary somatosensory cortex (S1) and motor cortex (M1) following whisker stimulation was assessed using in vivo Ca2+ imaging. CCI-induced changes in responses were analyzed. RESULTS: Before CCI, whisker stimulation induced a greater Ca2+ response in the contralateral S1 than in the ipsilateral S1 and contralateral M1. The peak Ca2+ response amplitude in the bilateral S1 and contralateral M1 decreased two days after CCI compared to before CCI. Decreased Ca2+ response amplitude in these regions was observed until four days after CCI. Seven days after CCI, the Ca2+ response amplitude in the contralateral S1 decreased, whereas that in the ipsilateral S1 and contralateral M1 recovered to control levels. CONCLUSION: These results suggest that neural activity in regions receiving excitatory inputs via corticocortical pathways recovers earlier than in regions receiving thalamocortical inputs. (185/250 words).
Subject(s)
Calcium , Disease Models, Animal , Mice, Transgenic , Motor Cortex , Somatosensory Cortex , Vibrissae , Animals , Motor Cortex/physiopathology , Somatosensory Cortex/physiopathology , Vibrissae/innervation , Vibrissae/physiology , Mice , Calcium/metabolism , Male , Neuralgia/physiopathology , Trigeminal Neuralgia/physiopathology , Trigeminal Neuralgia/metabolismABSTRACT
Layer 6 corticothalamic (L6 CT) neurons provide massive input to the thalamus, and these feedback connections enable the cortex to influence its own sensory input by modulating thalamic excitability. However, the functional role(s) feedback serves during sensory processing is unclear. One hypothesis is that CT feedback is under the control of extrasensory signals originating from higher-order cortical areas, yet we know nothing about the mechanisms of such control. It is also unclear whether such regulation is specific to CT neurons with distinct thalamic connectivity. Using mice (either sex) combined with in vitro electrophysiology techniques, optogenetics, and retrograde labeling, we describe studies of vibrissal primary motor cortex (vM1) influences on different CT neurons in the vibrissal primary somatosensory cortex (vS1) with distinct intrathalamic axonal projections. We found that vM1 inputs are highly selective, evoking stronger postsynaptic responses in CT neurons projecting to the dual ventral posterior medial nucleus (VPm) and posterior medial nucleus (POm) located in lower L6a than VPm-only-projecting CT cells in upper L6a. A targeted analysis of the specific cells and synapses involved revealed that the greater responsiveness of Dual CT neurons was due to their distinctive intrinsic membrane properties and synaptic mechanisms. These data demonstrate that vS1 has at least two discrete L6 CT subcircuits distinguished by their thalamic projection patterns, intrinsic physiology, and functional connectivity with vM1. Our results also provide insights into how a distinct CT subcircuit may serve specialized roles specific to contextual modulation of tactile-related sensory signals in the somatosensory thalamus during active vibrissa movements.
Subject(s)
Motor Cortex , Neural Pathways , Somatosensory Cortex , Thalamus , Vibrissae , Animals , Thalamus/physiology , Neural Pathways/physiology , Male , Motor Cortex/physiology , Female , Vibrissae/physiology , Somatosensory Cortex/physiology , Optogenetics , Neurons/physiology , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
Nasal chemosensation is considered the evolutionarily oldest mammalian sense and, together with somatosensation, is crucial for neonatal well-being before auditory and visual pathways start engaging the brain. Using anatomical and functional approaches in mice, we reveal that odor-driven activity propagates to a large part of the cortex during the first postnatal week and enhances whisker-evoked activation of primary whisker somatosensory cortex (wS1). This effect disappears in adult animals, in line with the loss of excitatory connectivity from olfactory cortex to wS1. By performing neonatal odor deprivation, followed by electrophysiological and behavioral work in adult animals, we identify a key transient regulation of nasal chemosensory information necessary for the development of wS1 sensory-driven dynamics and somatosensation. Our work uncovers a cross-modal critical window for nasal chemosensation-dependent somatosensory functional maturation.
Subject(s)
Nose , Olfactory Cortex , Somatosensory Cortex , Animals , Mice , Animals, Newborn , Mice, Inbred C57BL , Nose/physiology , Nose/anatomy & histology , Odorants , Olfactory Cortex/growth & development , Olfactory Cortex/physiology , Olfactory Cortex/ultrastructure , Sensory Deprivation/physiology , Smell/physiology , Somatosensory Cortex/growth & development , Somatosensory Cortex/physiology , Somatosensory Cortex/ultrastructure , Vibrissae/physiologyABSTRACT
To investigate which activity patterns in sensory cortex are relevant for perceptual decision-making, we combined two-photon calcium imaging and targeted two-photon optogenetics to interrogate barrel cortex activity during perceptual discrimination. We trained mice to discriminate bilateral whisker deflections and report decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3, with most neurons remaining silent during the task. Activating pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by optogenetic activation of non-coding neurons, which did not show sensory or motor-related activity during task performance. Photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results suggest that a pool of non-coding neurons, selectively suppressed by network inhibition during sensory processing, can be recruited to enhance perception.
Subject(s)
Neural Inhibition , Neurons , Optogenetics , Somatosensory Cortex , Vibrissae , Animals , Mice , Somatosensory Cortex/physiology , Vibrissae/physiology , Neural Inhibition/physiology , Neurons/physiology , Pyramidal Cells/physiology , Male , Photic Stimulation/methods , Mice, Inbred C57BLABSTRACT
Sensorimotor computation integrates bottom-up world state information with top-down knowledge and task goals to form action plans. In the rodent whisker system, a prime model of active sensing, evidence shows neuromodulatory neurotransmitters shape whisker control, affecting whisking frequency and amplitude. Since neuromodulatory neurotransmitters are mostly released from subcortical nuclei and have long-range projections that reach the rest of the central nervous system, mapping the circuits of top-down neuromodulatory control of sensorimotor nuclei will help to systematically address the mechanisms of active sensing. Therefore, we developed a neuroinformatic target discovery pipeline to mine the Allen Institute's Mouse Brain Connectivity Atlas. Using network connectivity analysis, we identified new putative connections along the whisker system and anatomically confirmed the existence of 42 previously unknown monosynaptic connections. Using this data, we updated the sensorimotor connectivity map of the mouse whisker system and developed the first cell-type-specific map of the network. The map includes 157 projections across 18 principal nuclei of the whisker system and neuromodulatory neurotransmitter-releasing. Performing a graph network analysis of this connectome, we identified cell-type specific hubs, sources, and sinks, provided anatomical evidence for monosynaptic inhibitory projections into all stages of the ascending pathway, and showed that neuromodulatory projections improve network-wide connectivity. These results argue that beyond the modulatory chemical contributions to information processing and transfer in the whisker system, the circuit connectivity features of the neuromodulatory networks position them as nodes of sensory and motor integration.
Subject(s)
Connectome , Vibrissae , Animals , Vibrissae/physiology , Vibrissae/innervation , Mice , Connectome/methods , Neural Pathways/physiology , Nerve Net/physiology , Mice, Inbred C57BL , MaleABSTRACT
Rapid eye movement (REM) sleep, also referred to as paradoxical sleep for the striking resemblance of its electroencephalogram (EEG) to the one observed in wakefulness, is characterized by the occurrence of transient events such as limb twitches or facial and rapid eye movements. Here, we investigated the local activity of the primary somatosensory or barrel cortex (S1) in naturally sleeping head-fixed male mice during REM. Through local field potential recordings, we uncovered local appearances of spindle waves in the barrel cortex during REM concomitant with strong delta power, challenging the view of a wakefulness-like activity in REM. We further performed extra- and intracellular recordings of thalamic cells in head-fixed mice. Our data show high-frequency thalamic bursts of spikes and subthreshold spindle oscillations in approximately half of the neurons of the ventral posterior medial nucleus which further confirmed the thalamic origin of local cortical spindles in S1 in REM. Cortical spindle oscillations were suppressed, while thalamus spike firing increased, associated with rapid mouse whisker movements and S1 cortical activity transitioned to an activated state. During REM, the sensory thalamus and barrel cortex therefore alternate between high (wake-like) and low (non-REM sleep-like) activation states, potentially providing a neuronal substrate for mnemonic processes occurring during this paradoxical sleep stage.