GABAergic interneurons have critical roles in signal processing in the cerebral cortex. Moreover, malfunction of these neurons has been implicated in a number of diseases ranging from epilepsy to schizophrenia, anxiety disorders and autism. The goal of Project 2 is to elucidate the functional roles of a group of neocortical GABAergic interneurons that express the ionotropic serotonin (5-HT) receptor 5HT3aR. 5HT3aRexpressing interneurons are the major population of GABAergic neurons in the superficial or associative layers of the cortex. However, largely as a result of the lack of experimental tools to identify and manipulate 5HT3aR interneurons litfie is known about the function of these cells in neocortical signal processing. Based on their location and prevalence, we hypothesize that 5HT3aR interneurons have crucial roles in sensory processing and in long-range interareal cortical communication. Moreover, studies indicate that all 5HT3aR neurons are potently modulated by 5-HT and acetylcholine (ACh) acting on ionotropic 5HT3a and nicotinic receptors, and that they are the main targets of the fast action of these neuromodulators in cortex, as well as of metabotropic responses in some 5HT3aR subpopulations. We hypothesize that these modulations are important in information processing and are involved in shaping cortical circuits during specific brain states and behavioral contexts. These observations have led to the overall hypothesis that 5HT3aR neurons have important roles in context-dependent sensory processing. This project will take advantage of new experimental reagents to begin testing these hypotheses. Electrophysiological recordings combined with optogenetic approaches will be used to study the functional connectivity of 5HT3aR neurons in primary somatosensory cortex with motor cortex and with the higher-order somatosensory thalamic nucleus, the posteromedial nucleus (POm). Photo-stimulation of channel rhodopsin expressing cholinergic and serotonergic axons will be used to study the modulation of 5HT3aR interneuron activity by these subcortical systems, and targeted-patch clamp recordings in-vivo will be used to study the changes in activity of 5HT3aR interneurons during different brain states and in response to sensory simulation and motor activity

Public Health Relevance

GABAergic INs is critical for the normal and pathological function of the brain. This Program Project will investigate the roles of 5HT3aR INs;the least understood but largest population of GABAergic neurons in superficial cortical layers, on the development, function, and plasticity of the cerebral cortex. This component of the PPG will study the connectivity, modulation and activity of 5HT3aR INs during different behavioral states to determine their role in context-dependent sensory processing.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
New York
United States
Zip Code
Tuncdemir, Sebnem N; Wamsley, Brie; Stam, Floor J et al. (2016) Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits. Neuron 89:521-35
Tremblay, Robin; Lee, Soohyun; Rudy, Bernardo (2016) GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits. Neuron 91:260-92
Ma, Lei; Qiao, Qian; Tsai, Jin-Wu et al. (2016) Experience-dependent plasticity of dendritic spines of layer 2/3 pyramidal neurons in the mouse cortex. Dev Neurobiol 76:277-86
Qiao, Qian; Ma, Lei; Li, Wei et al. (2016) Long-term stability of axonal boutons in the mouse barrel cortex. Dev Neurobiol 76:252-61
Petros, Timothy J; Bultje, Ronald S; Ross, M Elizabeth et al. (2015) Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate. Cell Rep 13:1090-5
Cichon, Joseph; Gan, Wen-Biao (2015) Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature 520:180-5
Tuncdemir, Sebnem N; Fishell, Gord; Batista-Brito, Renata (2015) miRNAs are Essential for the Survival and Maturation of Cortical Interneurons. Cereb Cortex 25:1842-57
Miyoshi, Goichi; Young, Allison; Petros, Timothy et al. (2015) Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons. J Neurosci 35:12869-89
De Marco García, Natalia V; Priya, Rashi; Tuncdemir, Sebnem N et al. (2015) Sensory inputs control the integration of neurogliaform interneurons into cortical circuits. Nat Neurosci 18:393-401
Mayer, Christian; Jaglin, Xavier H; Cobbs, Lucy V et al. (2015) Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries. Neuron 87:989-98

Showing the most recent 10 out of 23 publications