Shaul Hestrin

Graduate & Fellowship Program Affiliations

• Neurosciences

Web Site Links

• Hestrin's Lab

Research Interests

Functional Mapping of Neocortical Circuits

The main interest of my lab is to understand how the properties of neocortical neurons and circuits give rise to cortical activity. We use different experimental approaches to define the functional cell types forming local networks within the neocortex and determine their inter-connections and how external inputs interact with cortical networks. Our approach includes multiple whole-cell recordings, calcium imaging, two-photon imaging and optogenetic activation of 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

• D1-like dopamine receptor activation modulates GABAergic inhibition but not electrical coupling between neocortical fast-spiking interneurons. Towers SK, Hestrin S "J Neurosci" 2008 ; 10 (28) : 2633-41
• Background synaptic conductance and precision of EPSP-spike coupling at pyramidal cells. Zsiros V, Hestrin S "J Neurophysiol" 2005 ; 6 (93) : 3248-56
• Electrical synapses define networks of neocortical GABAergic neurons Hestrin, S., Galarreta, M. "Trends in Neurosciences" 2005 : (28) : 304-309
• Synchronous versus asynchronous transmitter release: a tale of two types of inhibitory neurons. Hestrin, S, Galarreta, M "Nature Neuroscience" 2005 ; 10 (8) : 1283-1284
• Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors. Galarreta M, Erdélyi F, Szabó G, Hestrin S "J Neurosci" 2004 ; 44 (24) : 9770-8