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A unique inhibitory interneuron that regulates sensory coding in neocortex

Award Number: F31NS120720
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2020
PERIOD OF PERFORMANCE END DATE: 09/29/2023

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A unique inhibitory interneuron that regulates sensory coding in neocortex - PROJECT SUMMARY The goal of this project is to investigate how the deepest layer in the neocortex can modulate sensory perception through a unique type of inhibitory interneuron. Almost all sensory information proceeds through the thalamus en route to the neocortex. Layer 6 (L6) corticothalamic (CT) neurons send massive feedback projections to the thalamus, and they also send ascending collaterals capable of strongly modulating the cortex itself. Recent indirect evidence suggests this modulation may occur through a distinct type of fast-spiking (FS), parvalbumin- expressing inhibitory interneuron that resides in upper L6 and uniquely sends axons into the upper layers where they presumably impart strong translaminar inhibition. Because the primary sensory pathway from the thalamus enters cortex most prominently in these zones, this wiring is suggestive of strong modulatory effects on sensory inputs and influence on perceptual processing. FS interneurons are critically involved in gamma oscillations and have been implicated in cognitive deficits (Carlen et al., 2012; Korotkova et al., 2010) and schizophrenia (Lewis et al., 2012). L6-CT cells have also been implicated in these disorders. The role of FS cells in gamma rhythms suggests that the L6 CT→FS connectivity may modulate the cortex by imposing synchrony on sensory input layers to influence perceptual processing. The central goal of this proposal is to determine how modulation of sensory information is implemented by intracortical L6-CT circuits, and how this inhibitory pathway participates in the perception of stimuli. Aim 1 is to determine the anatomical circuits by which CT cells can modulate sensory processing within cortex. Specifically, I will systematically determine the frequency and strength by which L6-FS interneurons connect to known neuron types across the layers of a cortical column. I will test the hypothesis that upper L6-FS cells form strong connections with specific neuronal subsets in the overlying cortical column, such as pyramidal cells in L2/3, 4, and 5, as well as L4-FS cells, and whether their extrinsic connectivity rules further distinguish this class from other FS cells. Aim 2 will test whether distinct groups of interneurons can coordinate rhythms in the overlying column. Specifically, this will test the hypotheses that translaminar FS cells of upper L6 contain unique intrinsic physiological properties that support the coordination of fast oscillatory rhythms, and mediates the network rhythmic activity observed in LFPs during CT-evoked gamma in vitro. Aim 3 will test the role of putative upper L6-FS cells in detection task performance and oscillatory activity in the awake behaving animal. This proposed investigation will illuminate important functions of a unique circuit, and in doing so will provide the applicant significant training in several critical in vitro and in vivo techniques. The valuable training provided by two Co-Sponsors with complementary expertise will be critical for in vitro circuit dissection and for demonstrating the behavioral relevance of those circuits in vivo.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$4,649 )
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/24/2024	NON-COMPETING CONTINUATION	-$4,649
														Subtotal = -$4,649

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	9/9/2022	NON-COMPETING CONTINUATION	$46,752
														Subtotal = $46,752

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/24/2021	NON-COMPETING CONTINUATION	$46,036
														Subtotal = $46,036

Issue Date FY: 2020 ( Subtotal = $45,520 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/23/2020	NEW	$0
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/23/2020	NEW	$45,520
														Subtotal = $45,520

Grand Total All Awards = $133,659

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A unique inhibitory interneuron that regulates sensory coding in neocortex

Award Number: F31NS120720

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2020

PERIOD OF PERFORMANCE END DATE: 09/29/2023

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