Perception and other cognitive functions such as planning, thought and learning reflect processing of complex information by the cerebral neocortex. Adaptive function depends critically on inputs from subcortical centers and on subsequent signal processing by appropriately organized cortical microcircuits. The proposed work asks how information is faithfully transferred from one part of the brain to the next and how signal-transforming feedforward networks become refined by developmental experience. Using the rodent whisker-to-barrel system, we will examine thalamocortical microcircuits in normally- reared animals and in animals raised with abnormal tactile experience produced by simple trimming of whisker hairs during early postnatal life. Using quantitative sensory physiology methods and single-cell recordings, including anatomical labeling of functionally characterized thalamocortical neurons, we will evaluate hypotheses derived from a long-standing model of thalamocortical function in somatosensory and visual systems. The model postulates that response tuning of cortical layer 4 neurons reflects specific thalamic inputs and that local circuitry dynamically adjusts receptive field properties by regulating overall network excitability. Specific experiments will investigate the innervation pattern of thalamocortical axons, their functional impact, and their experience-dependent developmental plasticity. Results are expected to establish key mechanisms of thalamocortical function and development shared by different systems in different species.

Public Health Relevance

Normal brain function depends critically on faithful transmission of information from one part of the brain to the next. Early postnatal experience influences the development of circuits that receive and process the signals. This research plan investigates sensory signaling and experience-dependent plasticity in order to understand how abnormally functioning cortical microcircuits might contribute to impairments in perceptual/motor and other cognitive behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019950-28
Application #
8242619
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
1983-07-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
28
Fiscal Year
2012
Total Cost
$324,778
Indirect Cost
$110,403
Name
University of Pittsburgh
Department
Biology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kwegyir-Afful, E E; Kyriazi, H T; Simons, D J (2013) Weaker feedforward inhibition accounts for less pronounced thalamocortical response transformation in mouse vs. rat barrels. J Neurophysiol 110:2378-92
Middleton, Jason W; Omar, Cyrus; Doiron, Brent et al. (2012) Neural correlation is stimulus modulated by feedforward inhibitory circuitry. J Neurosci 32:506-18
Shoykhet, Michael; Simons, Daniel J; Alexander, Henry et al. (2012) Thalamocortical dysfunction and thalamic injury after asphyxial cardiac arrest in developing rats. J Neurosci 32:4972-81
Middleton, Jason W; Kinnischtzke, Amanda; Simons, Daniel J (2010) Effects of thalamic high-frequency electrical stimulation on whisker-evoked cortical adaptation. Exp Brain Res 200:239-50
Khatri, Vivek; Bruno, Randy M; Simons, Daniel J (2009) Stimulus-specific and stimulus-nonspecific firing synchrony and its modulation by sensory adaptation in the whisker-to-barrel pathway. J Neurophysiol 101:2328-38
Lee, SooHyun; Carvell, George E; Simons, Daniel J (2008) Motor modulation of afferent somatosensory circuits. Nat Neurosci 11:1430-8
Temereanca, Simona; Brown, Emery N; Simons, Daniel J (2008) Rapid changes in thalamic firing synchrony during repetitive whisker stimulation. J Neurosci 28:11153-64
Kwegyir-Afful, Ernest E; Marella, Sashi; Simons, Daniel J (2008) Response properties of mouse trigeminal ganglion neurons. Somatosens Mot Res 25:209-21
Shoykhet, Michael; Simons, Daniel J (2008) Development of thalamocortical response transformations in the rat whisker-barrel system. J Neurophysiol 99:356-66
Simons, Daniel J; Carvell, George E; Kyriazi, Harold T et al. (2007) Thalamocortical conduction times and stimulus-evoked responses in the rat whisker-to-barrel system. J Neurophysiol 98:2842-7

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