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oai:dspace.mit.edu:1721.1/1635672025-11-06T03:04:21Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022

Harnett, Mark T. Tang, Vincent D. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 2025-11-05T19:35:09Z 2025-11-05T19:35:09Z 2025-05 2025-07-08T20:12:50.677Z https://hdl.handle.net/1721.1/163567 High-frequency burst firing occurs throughout the mammalian cortex in vivo, yet both the underlying mechanisms and functional roles of bursts are unclear. Burst firing in brain slices is strongly modulated by the activity of apical dendrites, which branch extensively in layer 1 (L1) and receive long-range inputs from higher-order cortical and thalamic areas. These properties suggest a powerful subcellular substrate by which single pyramidal neurons could multiplex bottom-up and top-down information via L1-independent tonic spikes and L1-dependent bursts, respectively, and have provided a basis for emerging theoretical models of cortical computation and learning. However, our understanding of burst firing and subcellular processing remains critically limited by a lack of evidence in awake animals. It is unclear whether burst firing a) is preferentially recruited by bottom-up versus top-down inputs, and b) requires apical dendritic engagement. To answer these questions, we performed high-density extracellular recordings in primary visual cortex of awake mice while presenting a battery of Gabor (bottom-up) and inverse (top-down) visual stimuli. We report widespread high-frequency bursts in L2/3 and L5 pyramidal neurons. Contrary to expectation, bursts exhibited extremely short response latencies, and were most strongly recruited by Gabor stimuli. We further tested the causal contribution(s) of apical dendrites to burst firing and top-down visual tuning via two optogenetic manipulations: direct L5 apical tuft inhibition and NDNF interneuron activation. Strikingly, L1 inhibition only modestly reduced the burst fraction, and did not differentially affect Gabor vs inverse responses. Taken together, these results challenge prevailing theories of apical dendritic involvement in burst spike generation and feedback visual tuning, and provide new biological constraints for future theoretical and experimental work. Ph.D. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ Top-down and bottom-up interactions for cortical bursting Thesis application/pdf Doctoral Doctor of Philosophy Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="23645118-3e64-482e-8a06-1a43e6ab5013"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Top-down and bottom-up interactions for cortical bursting</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2025-05</PublicationDate> <Authors> <Author> <DisplayName>Tang, Vincent D.</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>https://rightsstatements.org/page/InC-EDU/1.0/</License> <Abstract>High-frequency burst firing occurs throughout the mammalian cortex in vivo, yet both the underlying mechanisms and functional roles of bursts are unclear. Burst firing in brain slices is strongly modulated by the activity of apical dendrites, which branch extensively in layer 1 (L1) and receive long-range inputs from higher-order cortical and thalamic areas. These properties suggest a powerful subcellular substrate by which single pyramidal neurons could multiplex bottom-up and top-down information via L1-independent tonic spikes and L1-dependent bursts, respectively, and have provided a basis for emerging theoretical models of cortical computation and learning. However, our understanding of burst firing and subcellular processing remains critically limited by a lack of evidence in awake animals. It is unclear whether burst firing a) is preferentially recruited by bottom-up versus top-down inputs, and b) requires apical dendritic engagement. To answer these questions, we performed high-density extracellular recordings in primary visual cortex of awake mice while presenting a battery of Gabor (bottom-up) and inverse (top-down) visual stimuli. We report widespread high-frequency bursts in L2/3 and L5 pyramidal neurons. Contrary to expectation, bursts exhibited extremely short response latencies, and were most strongly recruited by Gabor stimuli. We further tested the causal contribution(s) of apical dendrites to burst firing and top-down visual tuning via two optogenetic manipulations: direct L5 apical tuft inhibition and NDNF interneuron activation. Strikingly, L1 inhibition only modestly reduced the burst fraction, and did not differentially affect Gabor vs inverse responses. Taken together, these results challenge prevailing theories of apical dendritic involvement in burst spike generation and feedback visual tuning, and provide new biological constraints for future theoretical and experimental work.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>