Michael J Higley, MD/PhD

Assistant Professor of Neurobiology; Primary Member, Program in Cellular Neuroscience, Neurodegeneration and Repair (CNNR); Member, Kavli Institute for Neuroscience

Research Interests

Autistic Disorder; Schizophrenia; Neurodegenerative Diseases

Research Organizations

Interdepartmental Neuroscience Program

Program in Cellular Neuroscience, Neurodegeneration and Repair

Research Summary

The neocortex plays a central role in the processing, storage, and retrieval of information necessary for sensory perception and higher cognitive abilities. These functions depend on the capability of individual neurons to perform complex computations through the compartmentalization of electrical and biochemical signaling within their dendritic arbors. Our goal is to understand how the dynamic interactions of excitatory, inhibitory, and neuromodulatory inputs within different subcellular domains influence the activity of single neurons and the local networks in which they participate. By combining an array of methods, including electrophysiology, multiphoton microscopy, and optogenetic manipulation of targeted neuronal populations, we are bridging the gaps between molecular, cellular, and systems neuroscience. With this multilevel approach, we hope to generate new insights into the neural mechanisms of complex behaviors and the pathophysiology of neuropsychiatric disorders including schizophrenia and autism.

Extensive Research Description

The neocortex plays a central role in the processing, storage, and retrieval of information necessary for sensory perception and higher cognitive abilities. These functions depend on the capability of individual neurons to perform complex computations through the compartmentalization of electrical and biochemical signaling within their dendritic arbors. Our goal is to understand how the dynamic interactions of excitatory, inhibitory, and neuromodulatory inputs within different subcellular domains influence the activity of single neurons and the local networks in which they participate. By combining an array of methods, including electrophysiology, multiphoton microscopy, and optogenetic manipulation of targeted neuronal populations, we are bridging the gaps between molecular, cellular, and systems neuroscience. With this multilevel approach, we hope to generate new insights into the neural mechanisms of complex behaviors and the pathophysiology of neuropsychiatric disorders including schizophrenia and autism.

  • Development, plasticity, and function of inhibitory GABAergic synapses. We are particularly interested in GABAergic inputs to neuronal dendrites.
  • Functional organization of neuronal circuits in mouse visual cortex.
  • Modulation of synaptic transmission by norepinephrine and acetylcholine.
  • Disruption of neocortical synapses and circuits in mouse models of autism and schizophrenia.

Selected Publications

  • Chiu CQ, Lur G, Morse TM, Carnevale NT, Ellis-Davies G, and Higley MJ. Compartmentalization of GABAergic inhibition by dendritic spines. Science, 340:759-62.
  • Higley MJ and Sabatini BL. Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors. Nature Neuroscience 13:958-66, 2010.
  • Higley MJ*, Soler-Llavina G*, and Sabatini BL. Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration. Nature Neuroscience,12:1121-28, 2009.
  • Higley MJ and Sabatini BL. Calcium signaling in dendrites and spines: practical and functional considerations. Neuron 59: 902-13, 2008.
  • Higley MJ and Contreras D. Cellular mechanisms of suppressive interactions between somatosensory responses in vivo. J. Neurophys. 97:647-58, 2007
  • Higley MJ and Contreras D. Balanced excitation and inhibition determine spike timing during frequency adaptation. J Neurosci 26: 448-57, 2006.

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Contact Info

Michael J Higley, MD/PhD
Lab Location
Boyer Center for Molecular Medicine
295 Congress Avenue, Ste 449

New Haven, CT 06510
Office Location
Boyer Center for Molecular Medicine
295 Congress Avenue, Ste 454E

New Haven, CT 06510
Mailing Address
Dept. of NeurobiologyPO Box 208001
New Haven, CT 06520

Higley Lab

Research Image 2

Cortical layer 2/3 pyramidal neuron filled with fluorescent indicator through the whole-cell recording pipette.

Research Image 3

Synaptic potential and associated Ca transient evoked by focal glutamate uncaging onto a dendritic spine.