The Hestrin Lab

We are studying how the properties of neocortical microcircuits give rise to cortical activity.

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 give 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.More recently we are using calcium imaging to study the activity of neocortical circuits. These methods allow us to monitor the activity of large number of neurons (100-1000 cells). 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.
Using these methods we have recently discovered that in addition to GABA releasing synaptic connections, inhibitory neurons are also connected via electrical synapses. These GABAergic and electrical synapses form networks of interconnected inhibitory neurons belonging to the same functional type. We provided evidence supporting the hypothesis that these networks are sensitive to the timing of action potentials in the cortex and can play a role in coordinating cortical activity.

Our current projects include:

i. Defining the functional cell types forming local networks within the neocortex and their inter-connections via chemical and electrical synapses.

ii. Understanding how spikes are processed by different types of cortical neurons and how their chemical and electrical synapses coordinate spike timing within the network.

iii. Study the roles of different classes of cells in microcircuits in an intact brain using two-photon imaging of calcium activity together with electrophysiological recordings.

Representative Publications

• Electrical synapses define networks of neocortical GABAergic neurons.(2005). Hestrin, S., & Galarreta, M. Trends in Neurosciences 28:304-309.

• Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells.(2005). Zsiros, V., & Hestrin,S. J Neurophysiol,93: 6: 3248-56.

• Synchronous versus asynchronous transmitter release: a tale of two types of inhibitory neurons.(2005).Hestrin, S., & Galarreta, M. Nat Neurosci. 8: 10: 1283-4.

• Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors. (2004). Galarreta, M., Erdélyi, F., Szabó, G., & Hestrin, S.J Neurosci. 24: 44: 9770-8

• Synaptic interactions of late-spiking neocortical neurons in layer 1.(2003).Chu, Z., Galarreta, M., & Hestrin, S. J Neurosci. 23: 1: 96-102

• Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex. (2002). Galarreta M.& Hestrin S. Proc Natl Acad Sci U S A. 99: 19: 12438-43.

• Spike Transmission and Synchrony Detection in Networks of GABAergic Interneurons. (2001). Galarreta, M. & Hestrin, S. SCIENCE, 292:2295-2299.

• Electrical Synapses Between GABA-Releasing Interneurons. (2001). Galarreta, M. & Hestrin, S. NATURE REVIEWS NEUROSCIENCE, 2:425-433.

• A network of Fast-Spiking Cells in the Neocortex Connected by Electrical Synapses. (1999). Galarreta, M., & Hestrin, S. NATURE 402:72-75.

•Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex. Galarreta, M., & Hestrin, S. (1998). NATURE NEUROSCIENCE. 1:587-594.