Topic: interneurons

Parvalbumin-positive GABAergic interneurons (PV-INs) provide inhibitory control of excitatory neuron activity, coordinate circuit function, and regulate behavior and cognition. PV-INs are uniquely susceptible to loss and dysfunction in traumatic brain injury (TBI) and epilepsy but the cause of this susceptibility is unknown. One hypothesis is that PV-INs use specialized metabolic systems to support their high-frequency action potential firing and that metabolic stress disrupts these systems, leading to their dysfunction and loss. Metabolism-based therapies can restore PV-IN function after inju

To form a coherent perception of the world around us, we are constantly processing and integrating sensory information from multiple modalities. In fact, when auditory and visual stimuli occur within ~100 ms of each other, individuals tend to perceive the stimuli as a single event, even though they occurred separately. In recent years, our lab, and others, have developed rat models of audiovisual temporal perception using behavioural tasks such as temporal order judgments (TOJs) and synchrony judgments (SJs). While these rodent models demonstrate metrics that are consistent with humans (e.g.,

Classification of neurons, long viewed as a fairly boring enterprise, has emerged as a major bottleneck in analysis of neural circuits. High throughput single cell RNA-seq has provided a new way to improve the situation. We initially applied this method to mouse retina, showing that its five neuronal classes (photoreceptors, three groups of interneurons, and retinal ganglion cells) can be divided into 130 discrete types. We then applied the method to other species including human, macaque, zebrafish and chick. With the atlases in hand, we are now using them to address questions about how retin

During sexual behavior, copulation related sensory information and modulatory signals from the brain must be integrated and converted into the motor and secretory outputs that characterize ejaculation (Lenschow and Lima, Current Opinion in Neurobiology, 2020). Studies in humans and rats suggest the existence of interneurons in the lumbar spinal cord that mediates that step: the spinal ejaculation generator (SEG). My work aimed at gaining mechanistic insights about the neuronal circuits controlling ejaculation thereby applying cutting-edge techniques. More specifically, we mapped anatomically a

Rapidly changing inputs such as visual scenes and auditory landscapes are transmitted over several synaptic interfaces and perceived with little loss of detail, but individual neurons are typically “noisy” and cortico-cortical connections are typically “weak”. To understand how information embodied in spike train is transmitted in a lossless manner, we focus on a single synaptic interface: between pyramidal cells and putative interneurons. Using arbitrary white noise patterns injected intra-cortically as photocurrents to freely-moving mice, we find that directly-activated cells exhibit precisi

Each spring, billions of Bogong moths escape hot conditions in different regions of southeast Australia by migrating over 1000 km to a limited number of cool caves in the Australian Alps, historically used for aestivating over the summer. At the beginning of autumn the same individuals make a return migration to their breeding grounds to reproduce and die. To steer migration Bogong moths sense the Earth’s magnetic field and correlate its directional information with visual cues. In this presentation, we will show that a critically important visual cue is the distribution of starlight within th

Basket cells are key GABAergic inhibitory interneurons that target the somata and proximal dendrites, enabling efficient control of the timing and rate of spiking of their postsynaptic targets. In all cortical circuits, there are two major types of basket cell that exhibit striking developmental, molecular, anatomical, and physiological differences. In this talk, I will discuss recent results that reveal the tightly coupled complementarity of these two key microcircuit regulatory modules, demonstrating a novel form of brain-state-specific segregation of inhibition during spontaneous behavior,

The construction of cortical circuits requires the precise formation of connections between excitatory and inhibitory neurons during early development. Multiple factors, including neurotransmitters, neuronal activity, and neuronal-glial interactions, shape how these critical circuits form. Disruptions of these early processes can disrupt circuit formation, leading to epilepsy and other neurodevelopmental disorders. Here, I will describe our work into understanding how prolonged post-natal astrocyte development in the cortex creates a permissive window for glutamate signaling that provides to

Neural codes, such as temporal codes (precisely timed spikes) and rate codes (instantaneous spike firing rates), are believed to be used in encoding sensory information into spike trains of cortical neurons. Temporal and rate codes co-exist in the spike train and such multiplexed neural code-carrying spike trains have been shown to be spatially synchronized in multiple neurons across different cortical layers during sensory information processing. Inhibition is suggested to promote such synchronization, but it is unclear whether distinct subtypes of interneurons make different contributions in

Inhibitory interneurons come in different classes and form intricate circuits. While our knowledge of these circuits has advanced substantially over the last decades, it is not fully understood how the structure of these circuits relates to their function. I will present some of our recent attempts to “understand” the structure of interneuron circuits by means of computational modeling. Surprisingly (at least for us), we found that prominent features of inhibitory circuitry can be accounted for by an optimisation for excitation-inhibition (E/I) balance. In particular, we find that such an opti

Temporal lobe epilepsy is associated with memory deficits but the circuit mechanisms underlying these cognitive disabilities are not understood. We used electrophysiological recordings, open-source wire-free miniaturized microscopy and computational modeling to probe these deficits in a model of temporal lobe epilepsy. We find desynchronization of dentate gyrus interneurons with CA1 interneurons during theta oscillations and a loss of precision and stability of place fields. We also find that emergence of place cell dysfunction is delayed, providing a potential temporal window for treatments.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we have adopted a symptom-to-circuit approach in theFmr1-/- mouse model of Fragile X syndrome (FXS). Using a go/no-go task and in vivo 2-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons in primary visual cortex, and a decrease in the activity of parvalbumin (PV) interneurons. Restoring visually evoked activity in PV cells in Fmr1-/- mice with a chemogenetic (DREADD) strategy was s

Inhibitory microcircuits play an important role regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration are gatekeepers for neural activity, synaptic plasticity and the formation of sensory representations. We have been investigating the synaptic plasticity mechanisms underlying the formation of ensembles in olfactory and orbitofrontal cortex. We have been focusing on the roles of three inhibitory neuron classes in gating excitatory synaptic plasticity in olfactory cortex- somatostatin (SST-INs), parvalbumin (PV-INs), and vasoactive intestin

Interneurons, ubiquitous in the central nervous system, form networks connected through both inhibitory chemical synapses and gap junctions. These networks are essential for regulating neuronal activity notably by regulating temporally patterned dynamic states. We aim to understand the mechanisms that allow for synchronization to arise in networks of interneurons with both chemical synapses and electrical gap junctions (Panel 1). To this end, we use the exact mean-field reduction, often referred to as the “neural mass model” in the literature (Montbrio et al, PRX, 2015). We first analyse a sin