Topic: GABAergic 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

GABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS). Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. We have investigated the emergence and plasticity of axo-axonic synapses in layer 2/3 of the somatosensory cortex (S1) and found that ChCs follow w

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in s

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in som

The inhibitory actions of the heterogeneous collection of GABAergic interneurons tremendously influence cortical information processing, which is reflected by diseases like autism, epilepsy and schizophrenia that involve defects in cortical inhibition. Apart from the regulation of physiological processes like synaptic transmission, proper interneuron function also relies on their correct development. Hence, decrypting regulatory networks that direct proper cortical interneuron development as well as adult functionality is of great interest, as this helps to identify critical events implicated

Dravet syndrome (DS) is a neurodevelopmental disorder caused by heterozygous loss-of-function of the gene SCN1A encoding the voltage-gated sodium channel subunit Nav1.1, and is defined by treatment-resistant epilepsy, intellectual impairment, and sudden death. However, disease mechanisms remain unclear, as previously-identified deficiency in action potential generation of Nav1.1-expressing parvalbumin-positive fast-spiking GABAergic interneurons (PV-INs) in DS (Scn1a+/-) mice normalizes during development. We used a novel approach that facilitated the assessment of PV-IN function at both early

Dravet syndrome is a severe childhood epilepsy due to heterozygous loss-of-function mutation of the gene SCN1A, which encodes the type 1 neuronal voltage gated sodium (Na+) channel alpha-subunit Nav1.1. Prior studies in mouse models of Dravet syndrome (Scn1a+/- mice) at early developmental time points indicate that, in cerebral cortex, Nav1.1 is predominantly expressed in GABAergic interneurons (INs) and, in particular, in parvalbumin-positive fast-spiking basket cells (PV-INs). This has led to a model of Dravet syndrome pathogenesis whereby Nav1.1 mutation leads to preferential IN dysfunction