Dysfunctions of the cerebral cortex, the highest-level processor of our sensations, perceptions, and decisions, are thought to underlie numerous neurological and psychiatric disorders. A major obstacle to treating such pathology is the high degree of complexity of cortical circuitry, which has remained largely enigmatic. Each primary sensory area of cortex receives connections from a primary and secondary thalamic nucleus. Strokes destroying primary thalamic nuclei cause near complete loss of sensation, but damage to secondary thalamus produces complex behavioral deficits. Secondary thalamus is also connected with diverse cortical areas, suggesting a possible role in psychiatric disorders. Nevertheless, the functions of secondary thalamus remain unknown. Are secondary nuclei alternate sensory pathways to cortex? Or key sources of behavioral signals? This project will focus on the secondary somatosensory thalamus (the posterior medial nucleus, POm). POm has sometimes been regarded as an afferent sensory pathway, operating in parallel with the primary thalamic relay, but several studies support the view that POm is instead downstream of primary somatosensory cortex. POm has been suspected of mediating communication between cortical areas and, more recently, to aggregate motor signals to provide as feedback to cortical areas. Like secondary visual thalamus, POm may also have a role in selectively enhancing particular stimuli. The first goal of this project is to investigate coding of sensory, motor and behavioral signals in POm. The second goal is to understand their functional impact on primary somatosensory cortex, particularly on apical dendrites in cortical layer 1-a major target of POm. The third goal is to determine whether or not simple sensory behaviors require POm. To achieve these goals, we will combine mouse behavior with electrophysiology, two-photon microscopy, and optogenetics.
We aim to identify the role of this long obscure circuit component in somatosensation. Identifying fundamental functions of this secondary thalamic nucleus will likely pave the way for future studies in other neocortical systems and in higher-order species.

Public Health Relevance

Dysfunctions of cerebral cortex and thalamus are thought to underlie numerous neurological and psychiatric disorders, but the behavioral and functional roles of secondary nuclei in thalamus remain unknown. Identifying their contributions to normal circuit function will lead to better treatment of pathological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS069679-10
Application #
9900071
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
2010-04-01
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
10
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurosciences
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Hong, Y Kate; Lacefield, Clay O; Rodgers, Chris C et al. (2018) Sensation, movement and learning in the absence of barrel cortex. Nature 561:542-546
Bouchard, Matthew B; Voleti, Venkatakaushik; Mendes, César S et al. (2015) Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics 9:113-119
Ramirez, Alejandro; Pnevmatikakis, Eftychios A; Merel, Josh et al. (2014) Spatiotemporal receptive fields of barrel cortex revealed by reverse correlation of synaptic input. Nat Neurosci 17:866-75
Schoonover, Carl E; Tapia, Juan-Carlos; Schilling, Verena C et al. (2014) Comparative strength and dendritic organization of thalamocortical and corticocortical synapses onto excitatory layer 4 neurons. J Neurosci 34:6746-58
Ma, Hongtao; Harris, Samuel; Rahmani, Redi et al. (2014) Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals. Neurophotonics 1:015003
Constantinople, Christine M; Bruno, Randy M (2013) Deep cortical layers are activated directly by thalamus. Science 340:1591-4
Oberlaender, Marcel; de Kock, Christiaan P J; Bruno, Randy M et al. (2012) Cell type-specific three-dimensional structure of thalamocortical circuits in a column of rat vibrissal cortex. Cereb Cortex 22:2375-91
Oberlaender, Marcel; Ramirez, Alejandro; Bruno, Randy M (2012) Sensory experience restructures thalamocortical axons during adulthood. Neuron 74:648-55
Constantinople, Christine M; Bruno, Randy M (2011) Effects and mechanisms of wakefulness on local cortical networks. Neuron 69:1061-8
Bruno, Randy M (2011) Synchrony in sensation. Curr Opin Neurobiol 21:701-8