Trigeminal Sensory Supply Is Essential for Motor Recovery after Facial Nerve Injury.

Recovery of mimic function after facial nerve transection is poor. The successful regrowth of regenerating motor nerve fibers to reinnervate their targets is compromised by (i) poor axonal navigation and excessive collateral branching, (ii) abnormal exchange of nerve impulses between adjacent regrowing axons, namely axonal crosstalk, and (iii) insufficient synaptic input to the axotomized facial motoneurons. As a result, axotomized motoneurons become hyperexcitable but unable to discharge. We review our findings, which have addressed the poor return of mimic function after facial nerve injuries, by testing the hypothesized detrimental component, and we propose that intensifying the trigeminal sensory input to axotomized and electrophysiologically silent facial motoneurons improves the specificity of the reinnervation of appropriate targets. We compared behavioral, functional, and morphological parameters after single reconstructive surgery of the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery, but combined with direct or indirect stimulation of the ipsilateral infraorbital nerve. We found that both methods of trigeminal sensory stimulation, i.e., stimulation of the vibrissal hairs and manual stimulation of the whisker pad, were beneficial for the outcome through improvement of the quality of target reinnervation and recovery of vibrissal motor performance.

Identification of a Developmental Switch in Information Transfer between Whisker S1 and S2 Cortex in Mice.

The whiskers of rodents are a key sensory organ that provides critical tactile information for animal navigation and object exploration throughout life. Previous work has explored the developmental sensory-driven activation of the primary sensory cortex processing whisker information (wS1), also called barrel cortex. This body of work has shown that the barrel cortex is already activated by sensory stimuli during the first postnatal week. However, it is currently unknown when over the course of development these stimuli begin being processed by higher-order cortical areas, such as secondary whisker somatosensory area (wS2). Here we investigate the developmental engagement of wS2 by whisker stimuli and the emergence of corticocortical communication from wS1 to wS2. Using in vivo wide-field imaging and multielectrode recordings in control and conditional KO mice of either sex with thalamocortical innervation defects, we find that wS1 and wS2 are able to process bottom-up information coming from the thalamus from birth. We also identify that it is only at the end of the first postnatal week that wS1 begins to provide functional excitation into wS2, switching to more inhibitory actions after the second postnatal week. Therefore, we have uncovered a developmental window when information transfer between wS1 and wS2 reaches mature function.SIGNIFICANCE STATEMENT At the end of the first postnatal week, the primary whisker somatosensory area starts providing excitatory input to the secondary whisker somatosensory area 2. This excitatory drive weakens during the second postnatal week and switches to inhibition in the adult.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases.

The effect of charge-balanced transcutaneous electrical nerve stimulation on rodent facial nerve regeneration.

This study aimed to investigate the effect of charge-balanced transcutaneous electrical nerve stimulation (cb-TENS) in accelerating recovery of the facial function and nerve regeneration after facial nerve (FN) section in a rat model. The main trunk of the left FN was divided and immediately sutured just distal to the stylomastoid foramen in 66 Sprague-Dawley rats. The control group had no electrical stimulus. The other two groups received cb-TENS at 20 Hz (20 Hz group) or 40 Hz (40 Hz group). Cb-TENS was administered daily for seven days and then twice a week for three weeks thereafter. To assess the recovery of facial function, whisker movement was monitored for four weeks. Histopathological evaluation of nerve regeneration was performed using transmission electron microscopy (TEM) and confocal microscopy with immunofluorescence (IF) staining. In addition, the levels of various molecular biological markers that affect nerve regeneration were analyzed. Whisker movement in the cb-TENS groups showed faster and better recovery than the control group. The 40 Hz group showed significantly better movement at the first week after injury (p < 0.0125). In histopathological analyses using TEM, nerve axons and Schwann cells, which were destroyed immediately after the injury, recovered in all groups over time. However, the regeneration of the myelin sheath was remarkably rapid and thicker in the 20 Hz and 40 Hz groups than in the control group. Image analysis using IF staining showed that the expression levels of S100B and NF200 increased over time in all groups. Specifically, the expression of NF200 in the 20 Hz and 40 Hz groups increased markedly compared to the control group. The real-time polymerase chain reaction was performed on ten representative neurotrophic factors, and the levels of IL-1ß and IL-6 were significantly higher in the 20 and 40 Hz groups than in the control group (p < 0.015). Cb-TENS facilitated and accelerated FN recovery in the rat model, as it significantly reduced the recovery time for the whisker movement. The histopathological study and analysis of neurotrophic factors supported the role of cb-TENS in the enhanced regeneration of the FN.

Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons.

Gaba-ergic neurons are a diverse cell class with extensive influence over cortical processing, but their role in experience-dependent plasticity is not completely understood. Here we addressed the role of cortical somatostatin- (SOM-INs) and vasoactive intestinal polypeptide- (VIP-INs) containing interneurons in a Pavlovian conditioning where stimulation of the vibrissae is used as a conditioned stimulus and tail shock as unconditioned one. This procedure induces a plastic change observed as an enlargement of the cortical functional representation of vibrissae activated during conditioning. Using layer-targeted, cell-selective DREADD transductions, we examined the involvement of SOM-INs and VIP-INs activity in learning-related plastic changes. Under optical recordings, we injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to the activated vibrissae. The activity of the interneurons was modulated during all conditioning sessions, and functional 2-deoxyglucose (2DG) maps were obtained 24 h after the last session. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation was absent. The behavioral effect of conditioning was disturbed. Both L4 SOM-INs excitation and L2/3 VIP-INs inhibition during conditioning did not affect the plasticity or the conditioned response. We found the activity of L4 SOM-INs is indispensable in the formation of learning-induced plastic change. We propose that L4 SOM-INs may provide disinhibition by blocking L4 parvalbumin interneurons, allowing a flow of information into upper cortical layers during learning.

Diversity of vibrissal follicle anatomy in cetaceans.

Most cetaceans are born with vibrissae but they can be lost or reduced in adulthood, especially in odontocetes. Despite this, some species of odontocetes have been found to have functioning vibrissal follicles (including the follicle itself and any remaining vibrissal hair shaft) that play a role in mechanoreception, proprioception and electroreception. This reveals a greater diversity of vibrissal function in odontocetes than in any other mammalian group. However, we know very little about vibrissal follicle form and function across the Cetacea. Here, we qualitatively describe the gross vibrissal follicle anatomy of fetuses of three species of cetaceans, including two odontocetes: Atlantic white-sided dolphin (Lagenorhynchus acutus), harbour porpoise (Phocoena phocoena), and one mysticete: minke whale (Balaenoptera acutorostrata), and compared our findings to previous anatomical descriptions. All three species had few, short vibrissae contained within a relatively simple, single-part follicle, lacking in muscles. However, we observed differences in vibrissal number, follicle size and shape, and innervation distribution between the species. While all three species had nerve fibers around the follicles, the vibrissal follicles of Balaenoptera acutorostrata were innervated by a deep vibrissal nerve, and the nerve fibers of the odontocetes studied were looser and more branched. For example, in Lagenorhynchus acutus, branches of nerve fibers travelled parallel to the follicle, and innervated more superficial areas, rather than just the base. Our anatomical descriptions lend support to the observation that vibrissal morphology is diverse in cetaceans, and is worth further investigation to fully explore links between form and function.

A model of lateral interactions as the origin of multiwhisker receptive fields in rat barrel cortex.

While cells within barrel cortex respond primarily to deflections of their principal whisker (PW), they also exhibit responses to non-principal, or adjacent, whiskers (AWs), albeit responses with diminished amplitudes and longer latencies. The origin of multiwhisker receptive fields of barrel cells remains a point of controversy within the experimental literature, with three contending possibilities: (i) barrel cells inherit their AW responses from the AW responses of thalamocortical (TC) cells within their aligned barreloid; (ii) the axons of TC cells within a barreloid ramify to innervate multiple barrels, rather than only terminating within their aligned barrel; (iii) lateral intracortical transmission between barrels conveys AW responsivity to barrel cells. In this work, we develop a detailed, biologically plausible model of multiple barrels in order to examine possibility (iii); in order to isolate the dynamics that possibility (iii) entails, we incorporate lateral connections between barrels while assuming that TC cells respond only to their PW and that TC cell axons are confined to their home barrel. We show that our model is capable of capturing a broad swath of experimental observations on multiwhisker receptive field dynamics within barrels, and we compare and contrast the dynamics of this model with model dynamics from prior work in which employ a similar general modeling strategy to examine possibility (i).

Transient expansion of the expression region of Hsd11b1, encoding 11ß-hydroxysteroid dehydrogenase type 1, in the developing mouse neocortex.

Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1; EC 1.1.1.146), encoded by Hsd11b1, is a key regulator of the local concentration of CORT/cortisol. Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles of Hsd11b1 in the developing mouse neocortex. Hsd11b1 was found mostly in pyramidal neurons. By retrograde tracing, we observed that some Hsd11b1-positive cells were projection neurons, indicating that at least some were excitatory. At postnatal day 0 (P0), Hsd11b1 was expressed in the deep layer of the somatosensory cortex. Then, from P3 to P8, the expression area expanded broadly; it was observed in layers 4 and 5, spanning the whole neocortex, including the primary motor cortex (M1) and the primary visual cortex (V1). The positive region gradually narrowed from P14 onwards and was ultimately limited to layer 5 of the somatosensory cortex at P26 and later. Furthermore, we administered CORT to nursing dams to increase the systemic CORT level of their pups. Here, we observed a reduced number of Hsd11b1-positive cells in the neocortex of these pups. Our observation suggests that Hsd11b1 expression in the developing neocortex is affected by systemic CORT levels. It is possible that stress on mothers influences the neocortical development of their children.

STDP and the distribution of preferred phases in the whisker system.

Rats and mice use their whiskers to probe the environment. By rhythmically swiping their whiskers back and forth they can detect the existence of an object, locate it, and identify its texture. Localization can be accomplished by inferring the whisker's position. Rhythmic neurons that track the phase of the whisking cycle encode information about the azimuthal location of the whisker. These neurons are characterized by preferred phases of firing that are narrowly distributed. Consequently, pooling the rhythmic signal from several upstream neurons is expected to result in a much narrower distribution of preferred phases in the downstream population, which however has not been observed empirically. Here, we show how spike timing dependent plasticity (STDP) can provide a solution to this conundrum. We investigated the effect of STDP on the utility of a neural population to transmit rhythmic information downstream using the framework of a modeling study. We found that under a wide range of parameters, STDP facilitated the transfer of rhythmic information despite the fact that all the synaptic weights remained dynamic. As a result, the preferred phase of the downstream neuron was not fixed, but rather drifted in time at a drift velocity that depended on the preferred phase, thus inducing a distribution of preferred phases. We further analyzed how the STDP rule governs the distribution of preferred phases in the downstream population. This link between the STDP rule and the distribution of preferred phases constitutes a natural test for our theory.

Functional and Structural Properties of Highly Responsive Somatosensory Neurons in Mouse Barrel Cortex.

Sparse population activity is a well-known feature of supragranular sensory neurons in neocortex. The mechanisms underlying sparseness are not well understood because a direct link between the neurons activated in vivo, and their cellular properties investigated in vitro has been missing. We used two-photon calcium imaging to identify a subset of neurons in layer L2/3 (L2/3) of mouse primary somatosensory cortex that are highly active following principal whisker vibrotactile stimulation. These high responders (HRs) were then tagged using photoconvertible green fluorescent protein for subsequent targeting in the brain slice using intracellular patch-clamp recordings and biocytin staining. This approach allowed us to investigate the structural and functional properties of HRs that distinguish them from less active control cells. Compared to less responsive L2/3 neurons, HRs displayed increased levels of stimulus-evoked and spontaneous activity, elevated noise and spontaneous pairwise correlations, and stronger coupling to the population response. Intrinsic excitability was reduced in HRs, while we found no evidence for differences in other electrophysiological and morphological parameters. Thus, the choice of which neurons participate in stimulus encoding may be determined largely by network connectivity rather than by cellular structure and function.

What we can and what we cannot see with extracellular multielectrodes.

Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable. We demonstrate this in the general setting of previously proposed kernel Current Source Density method and illustrate it with simplified examples as well as using evoked potentials from the barrel cortex obtained with a Neuropixels probe and with compatible model data. We show that with conceptual separation of the estimation space from experimental setup one can recover sources not accessible to standard methods.

Constructing an adult orofacial premotor atlas in Allen mouse CCF.

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors.

Rab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex.

Rab27a is an evolutionarily conserved small GTPase that regulates vesicle trafficking, and copy number variants of RAB27a are associated with increased risk of autism. However, the function of Rab27a on brain development is unknown. Here, we identified a form of paracrine communication that regulates spine development between distinct populations of developing cortical neurons. In the developing somatosensory cortex of mice, we show that decreasing Rab27a levels in late-born pyramidal neurons destined for layer (L) 2/3 had no cell-autonomous effect on their synaptic integration but increased excitatory synaptic transmission onto L4 neurons that receive somatosensory information. This effect resulted in an increased number of L4 neurons activated by whisker stimulation in juvenile mice. In addition, we found that Rab27a, the level of which decreases as neurons mature, regulates the release of small extracellular vesicles (sEVs) in developing neurons in vitro and decreasing Rab27a levels led to the accumulation of CD63-positive vesicular compartments in L2/3 neurons in vivo. Together, our study reveals that Rab27a-mediated paracrine communication regulates the development of synaptic connectivity, ultimately tuning responses to sensory stimulation, possibly via controlling the release of sEVs.

Distinct functional developments of surviving and eliminated presynaptic terminals.

For neuronal circuits in the brain to mature, necessary synapses must be maintained and redundant synapses eliminated through experience-dependent mechanisms. However, the functional differentiation of these synapse types during the refinement process remains elusive. Here, we addressed this issue by distinct labeling and direct recordings of presynaptic terminals fated for survival and for elimination in the somatosensory thalamus. At surviving terminals, the number of total releasable vesicles was first enlarged, and then calcium channels and fast-releasing synaptic vesicles were tightly coupled in an experience-dependent manner. By contrast, transmitter release mechanisms did not mature at terminals fated for elimination, irrespective of sensory experience. Nonetheless, terminals fated for survival and for elimination both exhibited developmental shortening of action potential waveforms that was experience independent. Thus, we dissected experience-dependent and -independent developmental maturation processes of surviving and eliminated presynaptic terminals during neuronal circuit refinement.

Cell-type-specific recruitment of GABAergic interneurons in the primary somatosensory cortex by long-range inputs.

Extensive hierarchical yet highly reciprocal interactions among cortical areas are fundamental for information processing. However, connectivity rules governing the specificity of such corticocortical connections, and top-down feedback projections in particular, are poorly understood. We analyze synaptic strength from functionally relevant brain areas to diverse neuronal types in the primary somatosensory cortex (S1). Long-range projections from different areas preferentially engage specific sets of GABAergic neurons in S1. Projections from other somatosensory cortices strongly recruit parvalbumin (PV)-positive GABAergic neurons and lead to PV neuron-mediated feedforward inhibition of pyramidal neurons in S1. In contrast, inputs from whisker-related primary motor cortex are biased to vasoactive intestinal peptide (VIP)-positive GABAergic neurons and potentially result in VIP neuron-mediated disinhibition. Regardless of the input areas, somatostatin-positive neurons receive relatively weak long-range inputs. Computational analyses suggest that a characteristic combination of synaptic inputs to different GABAergic IN types in S1 represents a specific long-range input area.

Excitatory neuronal CHD8 in the regulation of neocortical development and sensory-motor behaviors.

CHD8 (chromodomain helicase DNA-binding protein 8) is a chromatin remodeler associated with autism spectrum disorders. Homozygous Chd8 deletion in mice leads to embryonic lethality, making it difficult to assess whether CHD8 regulates brain development and whether CHD8 haploinsufficiency-related macrocephaly reflects normal CHD8 functions. Here, we report that homozygous conditional knockout of Chd8 restricted to neocortical glutamatergic neurons causes apoptosis-dependent near-complete elimination of neocortical structures. These mice, however, display normal survival and hyperactivity, anxiolytic-like behavior, and increased social interaction. They also show largely normal auditory function and moderately impaired visual and motor functions but enhanced whisker-related somatosensory function. These changes accompany thalamic hyperactivity, revealed by 15.2-Tesla fMRI, and increased intrinsic excitability and decreased inhibitory synaptic transmission in thalamic ventral posterior medial (VPM) neurons involved in somatosensation. These results suggest that excitatory neuronal CHD8 critically regulates neocortical development through anti-apoptotic mechanisms, neocortical elimination distinctly affects cognitive behaviors and sensory-motor functions in mice, and Chd8 haploinsufficiency-related macrocephaly might represent compensatory responses.

Neuronal Circuits in Barrel Cortex for Whisker Sensory Perception.

The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment. Rodents can use their whiskers to detect stimuli, distinguish textures, locate objects and navigate. Important aspects of whisker sensation are thought to result from neuronal computations in the whisker somatosensory cortex (wS1). Each whisker is individually represented in the somatotopic map of wS1 by an anatomical unit named a 'barrel' (hence also called barrel cortex). This allows precise investigation of sensory processing in the context of a well-defined map. Here, we first review the signaling pathways from the whiskers to wS1, and then discuss current understanding of the various types of excitatory and inhibitory neurons present within wS1. Different classes of cells can be defined according to anatomical, electrophysiological and molecular features. The synaptic connectivity of neurons within local wS1 microcircuits, as well as their long-range interactions and the impact of neuromodulators, are beginning to be understood. Recent technological progress has allowed cell-type-specific connectivity to be related to cell-type-specific activity during whisker-related behaviors. An important goal for future research is to obtain a causal and mechanistic understanding of how selected aspects of tactile sensory information are processed by specific types of neurons in the synaptically connected neuronal networks of wS1 and signaled to downstream brain areas, thus contributing to sensory-guided decision-making.

The follicle-sinus complex of the bottlenose dolphin (Tursiops truncatus). Functional anatomy and possible evolutional significance of its somato-sensory innervation.

Vibrissae are tactile hairs found mainly on the rostrum of most mammals. The follicle, which is surrounded by a large venous sinus, is called "follicle-sinus complex" (FSC). This complex is highly innervated by somatosensitive fibers and reached by visceromotor fibers that innervate the surrounding vessels. The surrounding striated muscles receive somatomotor fibers from the facial nerve. The bottlenose dolphin (Tursiops truncatus), a frequently described member of the delphinid family, possesses this organ only in the postnatal period. However, information on the function of the vibrissal complex in this latter species is scarce. Recently, psychophysical experiments on the river-living Guiana dolphin (Sotalia guianensis) revealed that the FSC could work as an electroreceptor in murky waters. In the present study, we analyzed the morphology and innervation of the FSC of newborn (n = 8) and adult (n = 3) bottlenose dolphins. We used Masson's trichrome stain and antibodies against neurofilament 200 kDa (NF 200), protein gene product (PGP 9.5), substance P (SP), calcitonin gene-related peptide, and tyrosine hydroxylase (TH) to characterize the FSC of the two age classes. Masson's trichrome staining revealed a structure almost identical to that of terrestrial mammals except for the fact that the FSC was occupied only by a venous sinus and that the vibrissal shaft lied within the follicle. Immunostaining for PGP 9.5 and NF 200 showed somatosensory fibers finishing high along the follicle with Merkel nerve endings and free nerve endings. We also found SP-positive fibers mostly in the surrounding blood vessels and TH both in the vessels and in the mesenchymal sheath. The FSC of the bottlenose dolphin, therefore, possesses a rich somatomotor innervation and a set of peptidergic visceromotor fibers. This anatomical disposition suggests a mechanoreceptor function in the newborns, possibly finalized to search for the opening of the mother's nipples. In the adult, however, this structure could change into a proprioceptive function in which the vibrissal shaft could provide information on the degree of rotation of the head. In the absence of psychophysical experiments in this species, the hypothesis of electroreception cannot be rejected.

Structural and functional organization of the lower jaw barrel subfield in rat primary somatosensory cortex.

Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened-cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear-shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel-free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO-staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel-specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel-free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization.

Developmental divergence of sensory stimulus representation in cortical interneurons.

Vasocative-intestinal-peptide (VIP+) and somatostatin (SST+) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Additionally, we find that Ca2+ signaling dynamics increase in precision as the cells and network mature. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ neurons at both time points. In addition, whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.