Shaul Hestrin

Graduate & Fellowship Program Affiliations

• Neurosciences

Current Research Interests

Functional Mapping of Neocortical Circuits

The main interest of my lab is to understand how the properties of neocortical neurons and the circuits they form give rise to cortical activity and function. Our approach includes recordings from multiple cells, calcium imaging, two-photon imaging and viral-based optogenetic methods to activate cortical neurons as well as cortical afferents.

The neocortex represents about 80% of the human brain and is associated with wide range of functions including sensory perception, motor movement, memory and higher aspects of cognition. Although cortical responses in anesthetized and behaving animals have been studied in some detail the microcircuitry that gives rise to these responses has not been understood. In the neocortex most of the synaptic connections that any cortical cell receives are from other cortical neurons. Thus, the interactions among cortical cells within the microcircuit play a critical role in determining cortical activity.

We have developed methods to define cell types using genetics and other means. We then use brain slices to record simultaneously from individual neurons that are synaptically connected. These methods allow us to characterize the wiring pattern of microcircuits and the synaptic properties of specific connections. We have used calcium imaging to monitor the activity of large number of neurons. These methods together with transgenic fluorescent labeling and targeted electrical recordings are used to study the roles of specific types of neurons in vitro and in vivo. More recently we have used optogenetic approaches to determine how external inputs affect the activity of cortical circuits.

Publications

• Cell-type identity: a key to unlocking the function of neocortical circuits. Brown SP, Hestrin S. Curr Opin Neurobiol. 2009; 19 (4): 415-21
• Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Brown SP, Hestrin S. Nature. 2009; 457 (7233): 1133-6
• D1-like dopamine receptor activation modulates GABAergic inhibition but not electrical coupling between neocortical fast-spiking interneurons. Towers SK, Hestrin S. J Neurosci. 2008; 28 (10): 2633-41
• Cannabinoid sensitivity and synaptic properties of 2 GABAergic networks in the neocortex. Galarreta M, Erdélyi F, Szabó G, Hestrin S. Cereb Cortex. 2008; 18 (10): 2296-305
• Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A, Buzsáki G, Cauli B, Defelipe J, Fairén A, Feldmeyer D, Fishell G, Fregnac Y, Freund TF, Gardner D, Gardner EP, Goldberg JH, Helmstaedter M, Hestrin S, Karube F, Kisvárday ZF, Lambolez B, Lewis DA, Marin O, Markram H, Muñoz A, Packer A, Petersen CC, Rockland KS, Rossier J, Rudy B, Somogyi P, Staiger JF, Tamas G, Thomson AM, Toledo-Rodriguez M, Wang Y, West DC, Yuste R. Nat Rev Neurosci. 2008; 9 (7): 557-68