The thalamus and neocortexare essential for normal sensation, movement, and cognition, and they work in intimate, inextricable association. The thalamus is the origin of virtually all specific information entering the neocortex, and the neocortex in turn sends massive feedback to the thalamus. Specific inhibitory neurons in both the thalamus and neocortex are critical regulators of information flow through the thalamocortical system. The central goal of my proposal is to understand the diverse functions of some of these inhibitory neurons and their synapses.There are four specific aims: 1) To characterize two distinctly different types of neocortical inhibitory intemeurons and their roles in the earliest stages of thalamocortical processing;2) To characterize the roles of these intemeurons in local circuits in the neocortex;3) To test the activity- and state-dependence of inhibitory functions;4) To characterize synaptic connections to, from, and within the thalamic reticular nucleus. We will use transgenic lines of mice to identify and select the neurons of interest, a variety of in vitro methods to recordfrom identified intemeurons, anatomical methods to verify and characterize neuron types, and pharmacological and molecular tools to manipulate cells and synapses. The proposed experiments will provide novel and important insight into the cellular mechanisms of inhibition in the thalamocortical system. This information will be of central importance to our understanding of the mechanisms of sensory, motor, and cognitive processing and their disorders. Description: The cerebral cortex and its partner, the thalamus, are brain regions critical for the most complex and uniquely human behaviors. Abnormalities of inhibitory nerve cells in the cortex and thalamus have been implicated in epilepsy, schizophrenia, anxiety, and other neurological and psychiatric diseases. The experiments proposed here will characterize the normal functions of inhibitory cells, so that their roles in disease can be more rationally evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS025983-20S1
Application #
7848395
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
1988-04-01
Project End
2010-08-31
Budget Start
2009-07-20
Budget End
2010-08-31
Support Year
20
Fiscal Year
2009
Total Cost
$16,308
Indirect Cost
Name
Brown University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Connors, Barry W (2017) Synchrony and so much more: Diverse roles for electrical synapses in neural circuits. Dev Neurobiol 77:610-624
Lee, Seung-Chan; Patrick, Saundra L; Richardson, Kristen A et al. (2014) Two functionally distinct networks of gap junction-coupled inhibitory neurons in the thalamic reticular nucleus. J Neurosci 34:13170-82
Cruikshank, Scott J; Ahmed, Omar J; Stevens, Tanya R et al. (2012) Thalamic control of layer 1 circuits in prefrontal cortex. J Neurosci 32:17813-23
Sills, Joseph B; Connors, Barry W; Burwell, Rebecca D (2012) Electrophysiological and morphological properties of neurons in layer 5 of the rat postrhinal cortex. Hippocampus 22:1912-22
Hayut, Itai; Fanselow, Erika E; Connors, Barry W et al. (2011) LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics. PLoS Comput Biol 7:e1002248
Fanselow, Erika E; Connors, Barry W (2010) The roles of somatostatin-expressing (GIN) and fast-spiking inhibitory interneurons in UP-DOWN states of mouse neocortex. J Neurophysiol 104:596-606
Connors, Barry W; Zolnik, Timothy A; Lee, Seung-Chan (2010) Enhanced functions of electrical junctions. Neuron 67:354-6
Lee, Seung-Chan; Cruikshank, Scott J; Connors, Barry W (2010) Electrical and chemical synapses between relay neurons in developing thalamus. J Physiol 588:2403-15
Cruikshank, Scott J; Urabe, Hayato; Nurmikko, Arto V et al. (2010) Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons. Neuron 65:230-45
Zhang, Jiayi; Laiwalla, Farah; Kim, Jennifer A et al. (2009) A microelectrode array incorporating an optical waveguide device for stimulation and spatiotemporal electrical recording of neural activity. Conf Proc IEEE Eng Med Biol Soc 2009:2046-9

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