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Behavioral and mechanistic dissection of a cognitive thalamo-cortical network

Award Number: R01MH120118
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/08/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Behavioral and mechanistic dissection of a cognitive thalamo-cortical network - Abstract Interactions between the cortex and thalamus are essential for sensation, action and cognition. Although the role of the thalamus in sensory processing is well-studied, its role in cognition is just beginning to be elucidated. This proposal will focus on the mediodorsal thalamus (MD), one of the largest thalamic nuclei of the mammalian brain, in regulating prefrontal cortex (PFC) activity in cognitive control and flexibility. MD-PFC interactions are known to be perturbed in schizophrenia, but therapeutic options are limited because the circuit mechanisms underlying these interactions are unknown. In this proposal, we will test an overarching model that the MD regulates PFC connectivity patterns to match the behavioral context through enhancement of context-relevant activity patterns and suppression of context-irrelevant ones. Specifically, our model posits that MD neurons generate context-specific signals by selectively strengthening PFC inputs that carry the basic elements of these signals but do not encode the context explicitly. Two MD cell types appear to generate such signals, one of which uses it to enhance context-congruent PFC activity while the other suppresses context incongruent activity. Lastly, our model posits that these distinct thalamic effects are mediated by different PFC circuit motifs, an excitatory/disinhibitory and an inhibitory, respectively. In Aim I, we will test the hypothesis that MD neurons generate context-specific output based on context non-specific inputs from PFC. In Aim II, we will test the hypothesis that the two MD functional cell types map onto distinct genetic types. In Aim III, we will test the hypothesis that the two MD-dependent effects on PFC, enhancement and suppression of activity patterns, are implemented by distinct local circuit motifs. Overall, our work should clarify the circuit mechanisms by which the MD influences PFC activity, providing a starting point for examining their generality across different task switching paradigms as well as relationship to higher order thalamus function more broadly. Our work should also be relevant to central mission of the NIH in understanding mechanisms with therapeutic potential.


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 = $517,222 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Mental Health Research Grants	001	5	7/5/2024	NON-COMPETING CONTINUATION	$51,722
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Mental Health Research Grants	000	5	1/19/2024	NON-COMPETING CONTINUATION	$465,500
														Subtotal = $517,222

Issue Date FY: 2023 ( Subtotal = $517,222 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Mental Health Research Grants	003	4	6/28/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$296,196
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Mental Health Research Grants	001	4	3/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$517,222
2023	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	3	3/21/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	002	3	6/28/2023	NON-COMPETING CONTINUATION	-$296,196
														Subtotal = $517,222

Issue Date FY: 2022 ( Subtotal = $472,083 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	3	5/23/2022	NON-COMPETING CONTINUATION	$47,208
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	3	1/18/2022	NON-COMPETING CONTINUATION	$424,875
														Subtotal = $472,083

Issue Date FY: 2021 ( Subtotal = $472,083 )
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	2	4/16/2021	NON-COMPETING CONTINUATION	$47,207
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	2	1/15/2021	NON-COMPETING CONTINUATION	$424,876
														Subtotal = $472,083

Issue Date FY: 2020 ( Subtotal = $496,930 )
2020	2020	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	2/6/2020	NEW	$496,930
														Subtotal = $496,930

Grand Total All Awards = $2,475,540

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Behavioral and mechanistic dissection of a cognitive thalamo-cortical network

Award Number: R01MH120118

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/08/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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