In the rodent vibrissal system, sensory processing is highly active and involves active communication between the barrel cortex and the vibrissal motor cortex. During task-dependent whisking behavior in vivo, GABAergic interneurons are more active. The activation of interneurons during active touch is responsible for sparse coding. Recruitment of interneurons, particularly layer 4 fast-spiking cells by TC inputs, has been well documented both in vitro and in vivo. However, no equivalent measurements have yet been reported for long-range M1 inputs within the sensory cortex. We therefore lack understanding of critical components of cortical computation. Our overarching goal is to construct a detailed circuit diagram, with detailed information at the level of specific inhibitory neurons and long-range synapses, to help understand the circuit basis underlying reciprocal sensorimotor associations within the S1 and M1.
In Aim 1, we will systematically compare properties M1 ?S1 projections in 5-HT3R, PV and SST expressing S1 interneurons.
In Aim 2, we will systematically compare properties S1?M1 projections in 5-HT3R, PV and SST expressing M1 interneurons.
Aim 3 will supplement Aims 1&2 and examine if there are any correlation between synaptic strength (mapping data, Aim 1&2) and firing (numbers and probabilities). The proposal will uncover network mechanisms underlying inhibitory contextual motor modulation of sensory processing and sensorimotor integration at motor cortex. This will allow us to gain better understanding about the nature of the excitation-inhibition balance in adult neurons and cellular mechanisms underlying long-range modulation of sensory and motor processing. Successful completion of this study will provide a comprehensive understanding of pathway, layer and cell-type specific nature of motor to sensory projections, and vice versa. This proposal will likely generate novel data and hypotheses for understanding sensory and motor circuit and neurological disorders with sensory-motor integration. Abnormal circuit wiring in cortical neurons is the key features of social and cognitive dysfunction such as epilepsy, autism and schizophrenia. Therefore, unveiling the cortical interneuronal circuit organization will also help o build the groundwork for future dissection of specific interneuronal types, synapses and circuits altered by mental diseases.

Public Health Relevance

This exploratory proposal will investigate GABAergic circuits underlying the reciprocal integration of long-range sensorimotor inputs. Our overarching goal is to establish a set of inhibitory cell-type specific operational rules regarding the regulation of feed-forward information within the sensorimotor circuit across large spatial scales.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS082958-01A1
Application #
8583267
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
2013-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$212,250
Indirect Cost
$62,250
Name
University of Wyoming
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
Wang, Xinjun; Hooks, Bryan M; Sun, Qian-Quan (2014) Thorough GABAergic innervation of the entire axon initial segment revealed by an optogenetic 'laserspritzer'. J Physiol 592:4257-76
Sun, Qian-Quan; Wang, Xinjun; Yang, Weiguo (2014) Laserspritzer: a simple method for optogenetic investigation with subcellular resolutions. PLoS One 9:e101600