GHOSH, Anirvan

Jan 06, 2011 08:25 PM

Incredibly smart:  UCSD

He is Stephen Kuffler Prof of Biology at UCSD.

Trained with Carla Shatz at Stfd from  1985 to 1991  (PhD in 91).

note bs in physics from  Cal Tech.

Post doc at Harvard Med .

The following is a summary of what his lab does at UCSD from the intro to The Ghosh Lab.

Resch aimed at understanding development and fxn of neural circuits.

Our research interests include the identification and characterization of genes that regulate synapse formation, function, and stability, and the investigation of molecular mechanisms underlying the activity-dependent development of

neuronal connections.

Perhaps the most remarkable feature of the developing brain is its ability to self-organize into functional circuits. How does this happen? We know that the formation of appropriate connections requires the targeting of axons and dendrites to specific regions of the brain and the selection of appropriate synaptic partners within those regions. Our lab is interested in understanding the mechanisms that mediate these decisions, and in the past few years we have identified a number of extracellular factors as well as transcription factors that regulate different aspects of hippocampal and cortical connectivity. The major areas of current research are described below.

Molec Mechs of  Synaptic specificity:

We are using the hippocampus as a model system to study the mechanisms of synaptic specificity because of its highly structured connectivity. We are using electrophysiological and molecular approaches to identify and characterize molecules that regulate synaptic specificity during establishment of neural circuits.

AMPA receptors :  role in stabilizing synapse development:

The establishment of functional neuronal circuits relies on the formation of excess synapses, followed by the elimination of inappropriate connections. Although the stabilization of presynaptic inputs is critical for the development and maintenance of functional circuits, the signals that regulate presynaptic stability are not known. We have found that synapse formation in cortical and hippocampal cultures is highly dynamic and involves the stabilization of a subset of synapses in a backdrop of a high rate of synapse formation and elimination. During the peak of synaptogenesis, only about 50% of putative synapses are stable over an hour.

REgulation of synaptic metaplasticity by calcium-dependent transcription

Once the initial connections are formed, neuronal activity exerts a major influence on the organization of neuronal circuits by regulating changes in synaptic strength. At many synapses, the direction and extent of change in synaptic strength depends on the stimulus parameters. For example, at the CA3-CA1 Schaffer collateral synapse in the hippocampus, low frequency stimulation leads to long term depression (LTD) and high frequency stimulation leads to long term potentiation (LTP). The relationship between stimulus frequency and change in synaptic strength is often depicted by a function called the Bienenstock, Cooper, Munro (BCM) function. This function itself can be modified by various manipulations, and the resulting shift in the BCM function is a measure of metaplasticity.

Functional analysis of cortical circuits

Another area of recent investigation in the lab is to use molecular genetic approaches to study the role of specific cell types in the development of cortical circuits. We are exploring the possibility that GABAergic inputs, which regulate postsynaptic depolarization with great spatial and temporal precision, may play a critical role in determining cortical connectivity by influencing input selectivity. GABAergic inputs are ideally suited to mediate input selectivity since different classes of GABAergic neurons innervate different parts of the principal (pyramidal) neurons and serve different functions. While the dendritic inhibitory inputs locally regulate the amplitude of excitatory postsynaptic potentials (EPSPs), the perisomatic inhibitory inputs regulate the overall firing rates of neurons. In principle each of these inputs could influence which excitatory inputs are stabilized, but whether they serve such a function is not known. By selectively silencing the activity of different GABAergic subpopulations we should be able to assess their contribution to the function of cortical circuits.

GHOSH, Anirvan

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