Parvalbumin Neurons Research Articles

Infralimbic parvalbumin neural activity facilitates cued threat avoidance

The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.

Infralimbic parvalbumin neural activity facilitates cued threat avoidance.

The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.

A sensory-motor-sensory circuit underlies antinociception ignited by primary motor cortex in mice.

A sensory-motor-sensory circuit underlies antinociception ignited by primary motor cortex in mice.

Rac1 in parvalbumin neurons of the medial prefrontal cortex governs rapid forgetting of social memory.

Social memory can undergo rapid forgetting at first according to the Ebbinghaus forgetting curve, for which the underlying mechanism remains entirely unknown. Here, we reported that rapid forgetting of social memory did not occur as indicated by social preference on stranger 2 (S2) over stranger 1 (S1) mouse, tested shortly after social interaction with S1. However, rapid forgetting of both social and object memories occurred as indicated by no social or object preference, respectively, when the constitutive active (CA) variant of Rac1 was knocked-in parvalbumin (PV) but not somatostatin (SST) neurons of the brain. Furthermore, rapid forgetting of only social memory occurred if this CA variant was knocked-in PV but not SST neurons of the medial prefrontal cortex (mPFC). By contrast, rapid forgetting of social memory was prevented by the dominant negative (DN) variant of Rac1 knocked-in PV neurons of the mPFC. Moreover, fiber photometry revealed that PV but not SST neurons of the mPFC generated dual calcium peaks to delineate each social interaction event. Thus, PV-specific Rac1 activity of the mPFC is both necessary and sufficient for controlling social behavior via rapid forgetting of social memory, providing a novel understanding of social behaviors under health and disease conditions.

The reuniens thalamus recruits recurrent excitation in the medial prefrontal cortex

The medial prefrontal cortex (mPFC) and hippocampus are critical for memory retrieval, decision making, and emotional regulation. While ventral CA1 (vCA1) shows direct and reciprocal connections with mPFC, dorsal CA1 (dCA1) forms indirect pathways to mPFC, notably via the thalamic reuniens nucleus (Re). Neuroanatomical tracing has documented structural connectivity of this indirect pathway through Re however, its functional operation is largely unexplored. Here, we used in vivo and in vitro electrophysiology along with optogenetics to address this question. Whole-cell patch-clamp recordings in acute mouse brain slices revealed both monosynaptic excitatory responses and disynaptic feedforward inhibition at Re-mPFC synapses. However, we also identified a prolonged excitation of mPFC by Re. These early monosynaptic and late recurrent components are in marked contrast to the primarily feedforward inhibition characteristic of thalamic inputs to the neocortex. Local field potential recordings in mPFC brain slices revealed prolonged synaptic activity throughout all cortical lamina upon Re activation, with the late excitation enhanced by blockade of parvalbumin neurons and GABAARs. In vivo Neuropixels recordings in head-fixed awake mice revealed a similar prolonged excitation of mPFC units by Re activation. In summary, Re output produces recurrent feedforward excitation within mPFC suggesting a potent amplification system in the Re-mPFC network. This may facilitate amplification of dCA1->mPFC signals for which Re acts as the primary conduit, as there is little direct connectivity. In addition, the capacity of mPFC neurons to fire bursts of action potentials in response to Re input suggests that these synapses have a high gain.

Inhibitory cell type heterogeneity in a spatially structured mean-field model of V1.

Inhibitory interneurons in the cortex are classified into cell types differing in their morphology, electrophysiology, and connectivity. Although it is known that parvalbumin (PV), somatostatin (SST), and vasoactive intestinal polypeptide-expressing neurons (VIP), the major inhibitory neuron subtypes in the cortex, have distinct modulatory effects on excitatory neurons, how heterogeneous spatial connectivity properties relate to network computations is not well understood. Here, we study the implications of heterogeneous inhibitory neurons on the dynamics and computations of spatially-structured neural networks. We develop a mean-field model of the system in order to systematically examine excitation-inhibition balance, dynamical stability, and cell-type specific gain modulations. The model incorporates three inhibitory cell types and excitatory neurons with distinct connectivity probabilities and recent evidence of long-range spatial projections of SST neurons. Position-dependent firing rate predictions are validated against simulations, and balanced solutions under Gaussian assumptions are derived from scaling arguments. Stability analysis shows that while long-range inhibitory projections in E-I circuits with a homogeneous inhibitory population result in instability, the heterogeneous network maintains stability with long-range SST projections. This suggests that a mixture of short and long-range inhibitions may be key to providing diverse computations while maintaining stability. We further find that conductance-based synaptic transmissions are necessary to reproduce experimentally observed cell-type-specific gain modulations of inhibition by PV and SST neurons. The mechanisms underlying cell-type-specific gain changes are elucidated using linear response theory. Our theoretical approach offers insight into the computational function of cell-type-specific and distance-dependent network structure.

Parvalbumin neurons mediate neurological phenotypes of anti-NMDAR encephalitis.

Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy individuals as a control. Daily administration of anti-NMDAR IgG into the medial prefrontal cortex (mPFC) of mice for 7 days resulted in cognitive impairments resembling clinical symptoms, which spontaneously resolved 30 days after discontinuing the injections. Immunohistochemical staining and electrophysiological testing of parvalbumin neurons in the mPFC treated with anti-NMDAR IgG revealed significant cellular morphological damage, reduced excitability, synaptic dysfunction and a loss of NMDAR antagonist-induced gamma oscillations. Application of optogenetic and pharmacogenetic techniques to activate parvalbumin neurons in the mPFC successfully reversed the cognitive impairments observed in the anti-NMDAR-IgG-treated mice. Single-cell sequencing of anti-NMDAR-IgG-treated parvalbumin neurons identified differentially expressed genes and pathways related to synapses and neuronal development, offering potential targets for therapeutic intervention. Additionally, we showed that these alterations in parvalbumin neurons were not confined to the mPFC, as similar changes were detected in the hippocampus after anti-NMDAR IgG injections. In summary, our findings elucidate distinct alterations in parvalbumin neurons during the pathogenesis of anti-NMDAR encephalitis, providing preclinical rationale for exploring approaches to modulate parvalbumin neuronal function to treat anti-NMDAR encephalitis.

Lateral inhibition in V1 controls neural and perceptual contrast sensitivity.

Lateral inhibition is a central principle in sensory system function. It is thought to operate by the activation of inhibitory neurons that restrict the spatial spread of sensory excitation. However, the neurons, computations and mechanisms underlying cortical lateral inhibition remain debated, and its importance for perception remains unknown. Here we show that lateral inhibition from parvalbumin neurons in mouse primary visual cortex reduced neural and perceptual sensitivity to visual contrast in a uniform subtractive manner, whereas lateral inhibition from somatostatin neurons more effectively changed the slope (or gain) of neural and perceptual contrast sensitivity. A neural circuit model, anatomical tracing and direct subthreshold measurements indicated that the larger spatial footprint for somatostatin versus parvalbumin synaptic inhibition explains this difference. Together, these results define cell-type-specific computational roles for lateral inhibition in primary visual cortex, and establish their unique consequences on sensitivity to contrast, a fundamental aspect of the visual world.

Distinct Patterns of PV and SST GABAergic Neuronal Activity in the Basal Forebrain during Olfactory-Guided Behavior in Mice.

Sensory perception relies on the flexible detection and interpretation of stimuli across variable contexts, conditions, and behavioral states. The basal forebrain (BF) is a hub for behavioral state regulation, supplying dense cholinergic and GABAergic projections to various brain regions involved in sensory processing. Of GABAergic neurons in the BF, parvalbumin (PV) and somatostatin (SST) subtypes serve opposing roles toward regulating behavioral states. To elucidate the role of BF circuits in sensory-guided behavior, we investigated GABAergic signaling dynamics during odor-guided decision-making in male and female mice. We used fiber photometry to record cell type-specific BF activity during an odor discrimination task and correlated temporal patterns of PV and SST neuronal activity with olfactory task performance. We found that while both PV-expressing and SST-expressing GABAergic neurons were excited during trial initiation, PV neurons were selectively suppressed by reward, whereas SST neurons were excited. Notably, chemogenetic inhibition of BF SST neurons modestly altered decision bias to favor reward seeking, while optogenetic inhibition of BF PV neurons during odor presentations improved discrimination accuracy. Together, these results suggest that the bidirectional activity of GABAergic BF neuron subtypes distinctly influence perception and decision-making during olfactory-guided behavior.

Cell-Type Specific Circuits in the Mammillary Body for Place and Object Recognition Memory.

Mammillary body (MB) is traditionally viewed as a structural node of an anatomic circuit for emotion and memory. However, little is known about its molecular and cellular organizations. Here, a discovery that MB contains four subtypes of neurons that occupy different spatial subregions is reported. Of these, two subtypes of neurons are tagged by parvalbumin (PV) and dopamine receptor-D2 (Drd2) markers. PV neurons are spontaneously active, whereas Drd2 neurons are inactive at rest and generate rebound bursts. These two distinct electrophysiological properties are encoded by Kcnn4 and Cacna1h. PV and Drd2 neurons generate two distinct cell-type specific circuits by receiving inputs from two discrete subiculum neuronal classes. Gain- and loss-of-function studies on these cortical-subcortical circuits demonstrate their differential roles for place and object recognition memory. This finding provides a comprehensive molecular and structural atlas of MB neurons at single-cell resolution and reveals that MB contains molecularly, structurally, and functionally dissociable streams within its serial architecture.

GluN2D-containing NMDA receptors in parvalbumin neurons in the nucleus accumbens regulate nocifensive responses in neuropathic pain.

GluN2D-containing NMDA receptors in parvalbumin neurons in the nucleus accumbens regulate nocifensive responses in neuropathic pain.

Transferring Mouse Emx1 and Emx2 Lentiviruses into the Chicken Embryonic Brain and Their Implication to the Organization and Evolution of the Amniote Pallium

Introduction: Homeobox genes are highly conserved and play critical roles in brain development. Recently, we have found that mammals have an additional fragment of approximately 20 amino acids in Emx1 and a poly-(AL)6-7 in Emx2, compared to other amniotes. It has been shown that Emx1 and Emx2 have synergistic actions in the brain development. These reports raise an interesting issue whether the differences of Emx1 and Emx2 between mammals and non-mammals are concerned with the organization and evolution of amniote pallium. Methods: Lentiviruses expressing mouse Emx1 and Emx2 (mEmx1/2) with additional fragments were injected into the ventricle of the chick telencephalon at embryonic day 3 to study the effects of mEmx1/2 on the development of chick pallium, whereas injections of lentiviruses containing chick Emx1 and Emx2 (cEmx1/2), no targeted gene insert or saline were as controls. The expressions of reelin, vimentin, GABA and MAP2, neurogenesis patterns for calbindin (CB) and parvalbumin (PV) neurons and the sizes of anterior commissure (AC) were then studied by immuohistochemical staining, and open-field tests were performed to assess locomotor activities and curious or exploratory behaviors of the chicks. Results: Following the injections of lentiviruses expressing mEmx1/2, the expressions of reelin, vimentin, GABA, and MAP2 increased in most parts of Wulst (W) and mesopallium (M), but not most of nidopallium (N). Neurogenesis patterns for CB and PV neurons changed toward mammalian inside-out one, and the sizes of AC staining for neurofilament were significantly larger. In addition, post-hatchling chicks showed higher rates of passive avoidance after training, but no significant differences in the total distance traveled and the percentage of time spent in the central rectangle, compared to those in the control groups. Conclusion: The present study indicated that mEmx1/2 had effects on the development of chick pallium, suggesting that they are probably involved in the organization and evolution of amniote pallium.

GABAB receptor-mediated potentiation of ventral medial habenula glutamatergic transmission in GABAergic and glutamatergic interpeduncular nucleus neurons.

The medial habenula (MHb)-interpeduncular nucleus (IPN) pathway plays an important role in information transferring between the forebrain and the midbrain. The MHb-IPN pathway has been implicated in the regulation of fear behavior and nicotine addiction. The synapses between the ventral MHb and the IPN show a unique property, i.e., an enhancement of synaptic transmission upon activation of GABAB receptors. This GABAB receptor-mediated potentiation of ventral MHb-IPN synaptic transmission has been implicated in regulating fear memory. Although IPN is known to contain parvalbumin (PV) and somatostatin (SST) GABAergic neurons and vesicular glutamate transporter 3 (VGLUT3)-expressing neurons, it is unknown how GABAB receptor activation affects ventral MHb-mediated glutamatergic transmission onto these three subtypes of IPN neurons. Our studies show robust glutamatergic connectivity from ventral MHb to PV and SST neurons in the IPN, while the ventral MHb-mediated glutamatergic transmission in IPN VGLUT3 neurons is weak. Although activation of GABAB receptors produces a robust potentiation of ventral MHb-mediated glutamatergic transmission in PV neurons, we observed a modest effect in IPN SST neurons. Despite the diminished basal synaptic transmission between ventral MHb and IPN VGLUT3 neurons, activation of GABAB receptors causes transient conversion of non-responding ventral MHb synapses into active synapses in some IPN VGLUT3 neurons. Thus, our results show strong ventral MHb connectivity to GABAergic IPN neurons compared to VGLUT3-expressing IPN neurons. Furthermore, GABAB receptor activation produces a differential effect on ventral MHb-mediated glutamatergic transmission onto PV, SST, and VGLUT3 neurons in the IPN.

Oxytocin modulates inhibitory balance in the prelimbic cortex to support social memory consolidation during REM sleep.

Rationale: The prelimbic cortex (PrL), enriched with oxytocin (OXT) receptors, plays a critical role in memory consolidation. However, the role of OXT in social memory consolidation within the PrL microcircuit remains poorly understood. Methods: To examine the role of OXT signaling in social memory consolidation, we used OXT biosensors and loss-of-function approaches, including tetanus toxin-mediated silencing of OXT neurons in the paraventricular nucleus (PVNOXT), optogenetic inhibition of the PVNOXT-PrL pathway during rapid-eye-movement (REM) sleep, and local administration of an OXT receptor antagonist in the PrL. In vivo molecular biosensors for vasoactive intestinal peptide (VIP), somatostatin, and presynaptic calcium imaging were employed to assess inhibitory signaling in the PrL microcircuit. Optogenetic activation of the PVNOXT-PrL pathway and intranasal OXT were used to evaluate resilience to chronic sleep deprivation-induced social memory deficits. Results: We identified that REM-sleep OXT release via the PVN to PrL pathway supports social memory consolidation. OXT signaling deficiency reduces the activity of VIP and parvalbumin (PV) neurons, thereby disrupting the inhibitory balance between somatic inhibition mediated by PV neurons and dendritic disinhibition mediated by VIP neurons in PrL microcircuits during REM sleep. Chronic sleep deprivation (SD) disrupts OXT release and inhibitory balance, leading to pyramidal neuron hyperactivity and social memory impairments. Notably, REM-sleep-specific activation of the PVNOXT-PrL pathway or intranasal OXT restores inhibitory balance and rescues social memory deficits in SD mice. Conclusion: Our results reveal how OXT modulates inhibitory balance in the PrL microcircuit to support social memory consolidation during REM sleep, suggesting potential therapeutic strategies for treating sleep-related memory disorders.

Elucidating the Pathophysiology of Various Diseases by Investigating the Role of Molecules in Brain Wiring

Semaphorins and their receptors plexins are axon guidance molecules that navigate axons to their final destinations during neural development. Semaphorins and plexins exert distinct roles in regulating biological functions such as the immune system and bone homeostasis. They also participate in the development and progression of various diseases such as osteoporosis and allergic diseases. This review describes the varied phenotypes revealed by the analysis of semaphorin or plexin knockout mice and discusses the association with pathogenesis and therapy of atherosclerosis, agenesis of the corpus callosum, and neuropsychiatric diseases. The deletion of semaphorin 4D in atherosclerosis-prone Apolipoprotein E-deficient mice mitigated atherosclerotic lesions, indicating its crucial involvement in the progression of atherosclerosis. Semaphorin 4D is also implicated in apoptosis induced by the estrogen-dependent generation of soluble semaphorin 4D and the active form of plexin-B1 in the postnatal vaginal opening in mice. Plexin-A1 knockout BALB/cA mice exhibited the agenesis of corpus callosum. This study indicates the crucial role of plexin-A1 in the midline crossing of callosal pioneer axons projecting from the cerebral cortex during the early phase of callosal formation. Adult plexin-A1-deficient mice exhibit reduced prepulse inhibition deficit, an endophenotype of schizophrenia, in addition to excessive self-grooming. Parvalbumin-expressing interneurons in the medial prefrontal cortex are significantly decreased in plexin-A1 knockout mice. In the parvalbumin neurons, oxidative stress is significantly increased in plexin-A1 knockout mice. Accordingly, plexin-A1 deficiency may augment oxidative stress in parvalbumin neurons, thereby impairing the parvalbumin neuron network and leading to behavioral abnormalities relevant to neuropsychiatric diseases.

From Play Date to Stress Fate: Juvenile Social Play Rescues Stress-Induced Changes in Adult Social Behavior.

Long-term effects of social play on neural and behavioral development remain unclear. We investigated whether just 1 h of juvenile social play could rescue the effects of play deprivation on stress-related behavior and markers of neural plasticity. Syrian hamsters were reared from postnatal days 21-43 in three conditions: peer isolation, peer isolation with daily social play sessions (dyadic play), or group-housed with littermates. In adulthood, subjects were exposed to acute social defeat stress, and we examined changes in perineuronal net (PNN) expression surrounding parvalbumin (PV) neurons in the prelimbic (PL), infralimbic (IL), and basolateral amygdala (BLA). Peer deprivation led to exaggerated submissive and defensive behavior in a conditioned defeat test, but 1 h of dyadic play rescued the heightened conditioned defeat response in both males and females. In females, play deprivation reduced PNN/PV coexpression in the PL and IL compared to control groups with opportunities for social play. Males exposed to peer isolation showed elevated agonistic behavior when returned to their littermates compared to males exposed to 1-h play encounters. These findings indicate juvenile social play has long-lasting effects on PNN expression surrounding PV cells in the medial prefrontal cortex, which allows for the development of species' typical agonistic behavior and greater stress resistance in adulthood. The ability of just 1 h of social play to rescue the effects of peer isolation highlights the powerful role of social interactions in neural and behavioral development.

Resilience to Alzheimer's disease associates with alterations in perineuronal nets.

Some individuals show intact cognition despite the presence of neuropathological hallmarks of Alzheimer's disease (AD). The plasticity of parvalbumin (PV)-containing interneurons might contribute to resilience. Perineuronal nets (PNNs), that is, extracellular matrix structures around neurons, modulate PV neuron function. We hypothesize that PNNs play a role in resilience to AD. PNN amount and morphology were determined in immunolabelled sections of the frontal cortex of control, AD and resilient subjects. Expression levels of genes related to PNNs and microglia signatures were evaluated by bulk RNA sequencing. The expression of the PNN-component aggrecan around PV neurons is decreased in resilient and AD subjects, whereas PNN-sugar chains are reduced only in resilient subjects. In AD, fewer presynaptic terminals on PV neurons are detected and genes related to PNN degradation are upregulated. These data show distinct PNN changes in individuals resilient to AD, which may contribute to preserved cognition despite the neuropathology. Aggrecan levels are decreased in the frontal cortex of AD and resilient subjects. In resilient subjects, WFA+ PNNs are reduced around neuronal somata. In AD patients, PV neurons show disrupted WFA peridendritic staining and synaptic loss. Expression levels of PNN-degrading enzymes are higher in AD. Excitatory neurons bearing a PNN show low amounts of ptau.

Perineuronal Nets on CA2 Pyramidal Cells and Parvalbumin-Expressing Cells Differentially Regulate Hippocampal-Dependent Memory.

Perineuronal nets (PNNs) are a specialized extracellular matrix that surrounds certain populations of neurons, including (inhibitory) parvalbumin (PV)-expressing interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells. To disentangle the specific roles of PNNs on CA2 pyramidal cells and PV neurons in behavior, we generated conditional knock-out mouse strains with the primary protein component of PNNs, aggrecan (Acan), deleted from either CA2 pyramidal cells (Amigo2 Acan KO) or from PV cells (PV Acan KO). Male and female animals of each strain were tested for social, fear, and spatial memory, as well as for reversal learning. We found that Amigo2 Acan KO animals, but not PV Acan KO animals, had impaired social memory and reversal learning. PV Acan KOs, but not Amigo2 Acan KOs, had impaired contextual fear memory. These findings demonstrate independent roles for PNNs on each cell type in regulating hippocampal-dependent memory. We further investigated a potential mechanism of impaired social memory in the Amigo2 Acan KO animals and found reduced input to CA2 from the supramammillary nucleus (SuM), which signals social novelty. Additionally, Amigo2 Acan KOs lacked a social novelty-related local field potential response, suggesting that CA2 PNNs may coordinate functional SuM connections and associated physiological responses to social novelty.

Chronic silencing of subsets of cortical layer 5 pyramidal neurons has a long-term influence on the laminar distribution of parvalbumin interneurons and the perineuronal nets.

Neural networks are established throughout cortical development, which require the right ratios of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron number and function can impede the development of GABAergic neurons, which can have long-lasting consequences on inhibitory networks. However, the role of deep-layer pyramidal neurons in instructing the development and distribution of GABAergic neurons is still unclear. To unravel the role of deep-layer pyramidal neuron activity in orchestrating the spatial and laminar distribution of parvalbumin neurons, we selectively manipulated subsets of layer 5 projection neurons. By deleting Snap25 selectively from Rbp4-Cre + pyramidal neurons, we abolished regulated vesicle release from subsets of cortical layer 5 projection neurons. Our findings revealed that chronically silencing subsets of layer 5 projection neurons did not change the number and distribution of parvalbumin neurons in the developing brain. However, it did have a long-term impact on the laminar distribution of parvalbumin neurons and their perineuronal nets in the adult primary motor and somatosensory cortices. The laminar positioning of parvalbumin neurons was altered in layer 4 of the primary somatosensory cortex in the adult Snap25 cKO mice. We discovered that the absence of layer 5 activity only had a transient effect on the soma morphology of striatal PV neurons during the third week of postnatal development. We also showed that the relationship between parvalbumin neurons and the perineuronal nets varied across different cortical layers and regions; therefore, their relationship is far more complex than previously described. The current study will help us better understand the bidirectional interaction between deep-layer pyramidal cells and GABAergic neurons, as well as the long-term impact of interrupting pyramidal neuron activity on inhibitory network formation.

Cortical dynamics in hand/forelimb S1 and M1 evoked by brief photostimulation of the mouse's hand.

Spiking activity along synaptic circuits linking primary somatosensory (S1) and motor (M1) areas is fundamental for sensorimotor integration in cortex. Circuits along the ascending somatosensory pathway through mouse hand/forelimb S1 and M1 were recently described in detail (Yamawaki et al., 2021). Here, we characterize the peripherally evoked spiking dynamics in these two cortical areas in the same system. Brief (5 ms) optogenetic photostimulation of the hand generated short (~25 ms) barrages of activity first in S1 (onset latency 15 ms) then M1 (10 ms later). The estimated propagation speed was 20-fold faster from hand to S1 than from S1 to M1. Response amplitudes in M1 were strongly attenuated to approximately a third of those in S1. Responses were typically triphasic, with suppression and rebound following the initial peak. Parvalbumin (PV) inhibitory interneurons were involved in each phase, accounting for three-quarters of the initial spikes generated in S1, and their selective photostimulation sufficed to evoke suppression and rebound in both S1 and M1. Partial silencing of S1 by PV activation during hand stimulation reduced the M1 sensory responses. These results provide quantitative measures of spiking dynamics of cortical activity along the hand/forelimb-related transcortical loop; demonstrate a prominent and mechanistic role for PV neurons in each phase of the response; and, support a conceptual model in which somatosensory signals reach S1 via high-speed subcortical circuits to generate characteristic barrages of cortical activity, then reach M1 via densely polysynaptic corticocortical circuits to generate a similar but delayed and attenuated profile of activity.