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The role of top-down dendritic processing in credit assignment and cortical dynamics

Award Number: R01MH135141
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/18/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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The role of top-down dendritic processing in credit assignment and cortical dynamics - Top-down regulation of cortical processing is critical for learning, attention, figure-ground separation, multisensory integration, contextual-modulation and many other processes associated with cognition. However, the biological mechanisms supporting top-down computation remain elusive. A popular and compelling hypothesis is that top-down computation is implemented via the engagement of apical tuft dendrites in layer 1. This hypothesis is indirectly supported by convergent anatomical and functional evidence, including observations in patients with disorders associated with disrupted top-down processing, but more direct evidence linking dendritic integration to top-down mechanisms is limited. To address this gap, we developed a novel imaging approach that allows simultaneous recording of somas and dendrites in large populations of neurons during learning, without signal contamination. We will combine this approach with two complementary behavioral tasks: a highly controlled Brain-Computer Interface (BCI) paradigm and a comparatively naturalistic virtual navigation task. Through the set of proposed experiments, we aim to test the overarching hypothesis that top-down computation is implemented via the engagement of apical tuft dendrites in layer 1, and that these signals are responsible for guiding learning in networks of neurons. We will do this by: (1) Establishing the relationship between single-neuron dendritic integration and circuit dynamics and studying the principles governing the changes in this relationship over the course of learning; (2) Interrogating the relationship between dendritic activity and behavioral variables, how this relationship is modified over the course of learning, and how dendrites instruct changes in their corresponding somas; and (3) Testing the hypothesis that dendrites receive vectorized error signals consistent with an efficient solution to the credit assignment problem. Results from these experiments will catalyze a new ways of thinking about cortical computation and learning principles in biological systems, propelling the field into new directions with impactful scientific and translational 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: 2026 ( Subtotal = $692,842 )
2026	2026	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	3	5/12/2026	NON-COMPETING CONTINUATION	$692,842
														Subtotal = $692,842

Issue Date FY: 2025 ( Subtotal = $692,842 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	2	4/17/2025	NON-COMPETING CONTINUATION	$588,915
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	003	2	5/22/2025	NON-COMPETING CONTINUATION	$103,927
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	002	1	5/15/2025	NEW	$0
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	4/16/2025	NEW	$0
														Subtotal = $692,842

Issue Date FY: 2024 ( Subtotal = $692,842 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	7/18/2024	NEW	$692,842
														Subtotal = $692,842

Grand Total All Awards = $2,078,526

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The role of top-down dendritic processing in credit assignment and cortical dynamics

Award Number: R01MH135141

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/18/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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