Feed-forward inhibitory circuits are a major source of synaptic inhibition to cortical neurons. The specific means by which they control the activity of cortical neurons is, however, poorly understood. The goal of this proposal is to address the mechanism by which feed-forward inhibitory circuits activated by thalamic afferents control the excitability of cortical neurons. We will test the hypothesis that thalamo-cortical feed-forward inhibition reduces the integration time window of cortical neurons, and enforces temporal fidelity of signal transmission between the thalamus and the cortex. This proposal has two aims:
Aim 1 addresses the role of thalamo-cortical feed-forward inhibition in controlling the integration time window and spike timing of cortical neurons.
Aim 2 addresses the cellular mechanism of thalamo-cortical feed-forward inhibition. The experiments will be performed on acute mouse thalamo-cortical slices using electrophysiological and morphological techniques. This study will provide insight into the functional role of feed-forward inhibition and the mechanisms by which neuronal networks balance excitation with synaptic inhibition. A deeper understanding of the mechanisms that control cortical excitability may contribute to the development of therapies aimed at preventing epileptogenesis in cortical areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH070058-03
Application #
7059469
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Glanzman, Dennis L
Project Start
2004-07-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$267,170
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Bagnall, Martha W; Hull, Court; Bushong, Eric A et al. (2011) Multiple clusters of release sites formed by individual thalamic afferents onto cortical interneurons ensure reliable transmission. Neuron 71:180-94
Adesnik, Hillel; Scanziani, Massimo (2010) Lateral competition for cortical space by layer-specific horizontal circuits. Nature 464:1155-60
Apicella, Alfonso; Yuan, Qi; Scanziani, Massimo et al. (2010) Pyramidal cells in piriform cortex receive convergent input from distinct olfactory bulb glomeruli. J Neurosci 30:14255-60
Hull, Court; Adesnik, Hillel; Scanziani, Massimo (2009) Neocortical disynaptic inhibition requires somatodendritic integration in interneurons. J Neurosci 29:8991-5
Hull, Court; Isaacson, Jeffry S; Scanziani, Massimo (2009) Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs. J Neurosci 29:9127-36
Glickfeld, Lindsey L; Atallah, Bassam V; Scanziani, Massimo (2008) Complementary modulation of somatic inhibition by opioids and cannabinoids. J Neurosci 28:1824-32
Kapfer, Christoph; Glickfeld, Lindsey L; Atallah, Bassam V et al. (2007) Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex. Nat Neurosci 10:743-53
Glickfeld, Lindsey L; Scanziani, Massimo (2006) Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells. Nat Neurosci 9:807-15
Feller, Marla B; Scanziani, Massimo (2005) A precritical period for plasticity in visual cortex. Curr Opin Neurobiol 15:94-100
Gabernet, Laetitia; Jadhav, Shantanu P; Feldman, Daniel E et al. (2005) Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition. Neuron 48:315-27