Interneurons

In the CA1 hippocampus, vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a prominent role in disinhibitory circuit motifs. However, the specific behavioral conditions that lead to circuit disinhibition remain uncertain. To investigate the behavioral relevance of VIP-IN activity, we employed wireless technologies allowing us to monitor and manipulate their function in freely behaving mice. Our findings reveal that, during spatial exploration in new environments, VIP-INs in the CA1 hippocampal region become highly active, facilitating the rapid encoding of novel spatial information...

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors. In this study, we ask whether this negative interaction can also be mimicked in experimental tau models of AD and whether the underlying mechanism can be understood...

Hippocampal pyramidal neuronal activity has been previously studied using conventional patch clamp in isolated cells and brain slices. We here introduce the loose patch clamping study of voltage-activated currents from in situ pyramidal neurons in murine cornus ammonis 1 hippocampal coronal slices. Depolarizing pulses of 15-ms duration elicited early transient inward, followed by transient and prolonged outward currents in the readily identifiable junctional region between the stratum pyramidalis (SP) and oriens (SO) containing pyramidal cell somas and initial segments...

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas...

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in developmental-behavioral inhibition, resulting in impulsivity and hyperactivity. Recent research has underscored cortical inhibition deficiencies in ADHD via the gamma-aminobutyric acid (GABA)ergic system, which is crucial for maintaining excitatory-inhibitory balance in the brain. This study explored postnatal changes in parvalbumin (PV) immunoreactivity, indicating GABAergic interneuron types, in the prefrontal (PFC) and motor (MC) cortices of spontaneously hypertensive rats (SHRs), an ADHD animal model...

Synchronous neuronal activity is a hallmark of the developing brain. In the mouse cerebral cortex, activity decorrelates during the second week of postnatal development, progressively acquiring the characteristic sparse pattern underlying the integration of sensory information. The maturation of inhibition seems critical for this process, but the interneurons involved in this crucial transition of network activity in the developing cortex remain unknown. Using in vivo longitudinal two-photon calcium imaging during the period that precedes the change from highly synchronous to decorrelated activity, we identify somatostatin-expressing (SST+) interneurons as critical modulators of this switch in mice...

Continuity of behaviors requires animals to make smooth transitions between mutually exclusive behavioral states. Neural principles that govern these transitions are not well understood. Caenorhabditis elegans spontaneously switch between two opposite motor states, forward and backward movement, a phenomenon thought to reflect the reciprocal inhibition between interneurons AVB and AVA. Here, we report that spontaneous locomotion and their corresponding motor circuits are not separately controlled. AVA and AVB are neither functionally equivalent nor strictly reciprocally inhibitory...

Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems combine such information. Here in mice, we used a combination of stereo photogrammetry for 3D reconstruction of the whisker array, brain-wide anatomical tracing and functional connectivity analysis to explore the possibility of tacto-visual convergence in sensory space and within the circuitry of the primary visual cortex (VISp). Strikingly, we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a tacto-visual sub-region of VISp whose visual space representation closely overlaps with the whisker search space...

Cortical dynamics and computations are strongly influenced by diverse GABAergic interneurons, including those expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP). Together with excitatory (E) neurons, they form a canonical microcircuit and exhibit counterintuitive nonlinear phenomena. One instance of such phenomena is response reversal, whereby SST neurons show opposite responses to top-down modulation via VIP depending on the presence of bottom-up sensory input, indicating that the network may function in different regimes under different stimulation conditions...

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of FoxG1 expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in FoxG1 expression levels during interneuron specification and migration...

Inflammation, reduced gamma-aminobutyric acidergic (GABAergic) function and altered neuroplasticity are co-occurring pathophysiologies in major depressive disorder (MDD). However, the link between these biological changes remains unclear. We hypothesized that inflammation induces deficits in GABAergic interneuron markers and that this effect is mediated by brain-derived neurotrophic factor (BDNF). We report here that systemic inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) (0.125, 0...

UNLABELLED: Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output...

Transcranial ultrasound activates mechanosensitive cellular signaling and modulates neural dynamics. Given that intrinsic neuronal activity is limited to a couple hundred hertz and often exhibits frequency preference, we examined whether pulsing ultrasound at physiologic pulse repetition frequencies (PRFs) could selectively influence neuronal activity in the mammalian brain. We performed calcium imaging of individual motor cortex neurons, while delivering 0.35 MHz ultrasound at PRFs of 10, 40, and 140 Hz in awake mice...

UNLABELLED: GABA A receptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG; however, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity...

GABAergic interneuron deficits have been implicated in the epileptogenesis of multiple neurological diseases. While epileptic seizures are a key clinical hallmark of CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), the etiology of these seizures remains elusive. Given that Cln2 R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical interneuron populations, we hypothesized that those two events might be causally related...

UNLABELLED: The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6...

UNLABELLED: The Cre-lox system is an indispensable tool in neuroscience research for targeting gene deletions to specific cellular populations. Here we assess the utility of several transgenic Cre lines, along with a viral approach, for targeting cerebellar Purkinje cells. Using a combination of a fluorescent reporter line ( Ai14 ) to indicate Cre -mediated recombination and a floxed Dystroglycan line ( Dag1 flox ) we show that reporter expression does not always align precisely with loss of protein...

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry and is likely involved in behavioral modulation and sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of sensorimotor processing, yet the role of POm-striatal projections has remained undetermined. Using optogenetics with slice electrophysiology, we found that POm provides robust synaptic input to direct and indirect pathway striatal spiny projection neurons (D1- and D2-SPNs, respectively) and parvalbumin-expressing fast spiking interneurons (PVs)...

UNLABELLED: The pregnancy hormone, human chorionic gonadotropin (hCG) is an immunoregulatory and neurotrophic glycoprotein of potential clinical utility in the neonate at risk for cerebral injury. Despite its well-known role in its ability to modulate the innate immune response during pregnancy, hCG has not been demonstrated to affect the pro-degenerative actions of inflammation in neonatal hypoxia-ischemia (HI). Here we utilize a neonatal mouse model of mild HI combined with intraperitoneal administration of lipopolysaccharide (LPS) to evaluate the neuroprotective actions of hCG in the setting of endotoxin-mediated systemic inflammation...

The morpho-functional properties of neural networks constantly adapt in response to environmental stimuli. The olfactory bulb is particularly prone to constant reshaping of neural networks because of ongoing neurogenesis. It remains unclear whether the complexity of distinct odor-induced learning paradigms and sensory stimulation induces different forms of structural plasticity. In the present study, we automatically reconstructed spines in 3D from confocal images and performed unsupervised clustering based on morphometric features...