Biophysics, Dendrites & Neural Computation
Our laboratory studies how the biophysical features of individual neurons endow neural circuits with powerful processing capabilities, ultimately facilitating the complex computations required to drive adaptive behavior. A principal focus of our work is the role of dendrites, the elaborate tree-like structures where neurons receive the vast majority of afferent input. The spatial arrangement of synaptic contacts on dendrites and the interaction of various biophysical mechanisms enable complex integration of synaptic inputs – our hypothesis is that circuit-level computations are built out of these fundamental operations.
The morphological features and local ion channel mechanisms in specific dendritic compartments strongly influence how neurons integrate their inputs. We combine brain slice electrophysiology, two-photon imaging, and biophysical modeling to investigate the rules and mechanisms supporting different forms of input-output processing across mammalian species.
How do biophysical mechanisms influence circuit-level computation during behavior? To address this question, we combine 2-photon imaging and multi-unit electrophysiological recording techniques with novel rodent behavioral paradigms to measure the activity of neuronal populations including subcellular compartments. This allows us to evaluate the engagement of dendritic mechanisms as a function of circuit dynamics during complex behaviors. These experiments are complemented by detailed anatomical and single-cell physiological investigations in brain slices.
Head direction is critical for efficient navigation and provides an experimentally tractable system with which to study multimodal integration in neural circuits. We use state-of-the-art chronic tetrode implants to record HD activity while mice perform goal-directed navigation in darkness and reorient to visual landmarks. These experiments are combined with anatomical, physiological, and optogenetic techniques, as well as novel behavioral and computational methods, to dissect the cellular and circuit architecture of head direction representations.
Ranganathan GN, Apostolides PF, Harnett MT, Xu NL, Druckmann S, Magee JC (2018). Active dendritic integration and mixed neocortical network representations during an adaptive sensing behavior. Nature Neuroscience 21(11):1583-90
Beaulieu-Laroche L, Toloza EHS, van der Goes MS, Lafourcade M, Barnagian D, Williams ZM, Eskandar EN, Frosch MP, Cash SS, Harnett MT (2018). Enhanced dendritic compartmentalization in human cortical neurons. Cell 175(3):643-651
Beaulieu-Laroche L & Harnett MT (2018). Dendritic Spines Prevent Synaptic Voltage Clamp. Neuron 97(1):75-82
Shin Yim Y, Park A, Berrios J, Lafourcade M, Pascual LM, Soares N, Yeon Kim J, Kim S, Kim H, Waisman A, Littman DR, Wickersham IR, Harnett MT, Huh JR, Choi GB (2017). Reversing behavioural abnormalities in mice exposed to maternal inflammation. Nature 549(7673):482-487
Harnett MT, Magee JC, Williams SR (2015). Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons. Journal of Neuroscience 35(3):1024-37
Harnett MT, Xu N, Magee JC, Williams SR (2013). Potassium channels control the interaction between active dendritic integration compartments in layer 5 cortical pyramidal neurons. Neuron 79(3):516-29 *Preview article in Neuron by Dax Hoffman, p409
Marvin JS, Borghuis BG, Tian L, Cichon J, Harnett MT, Akerboom J, Gordus A, Renninger SL, Chen T, Bargmann CI, Orger MB, Schreiter ER, Demb JB, Gan W, Hires SA, Looger LL (2013). An optimized fluorescent probe for visualizing glutamate neurotransmission. Nature Methods 10(2):162-70
Xu N, Harnett MT, Williams SR, Huber D, O’Connor, DH, Svoboda K, Magee JC (2012). Nonlinear dendritic integration of sensory and motor input produces an object localization signal. Nature 492(7428):247-51
Harnett MT*, Makara J*, Kath W, Spruston N, Magee JC (2012). Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491(7425):599-602