Functional biochemical compartmentilization in aspiny neurons

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Nerve cells are connected to each other by tiny contacts, called synapses. The majority of excitatory synapses in the brain are formed onto highly specialized cellular structures known as dendritic spines. It is generally accepted that every spine forms at least one synapse and represents a distinct biochemical compartment operating independently from neighboring synapses. Surprisingly, about one third of neurons in the brain lack spines and receive excitatory afferents directly onto the dendritic shaft. While signal transduction in this case presumes a certain degree of cross talk among individual synapses, this does not happen and synaptic communication in aspiny neurons remains confined to activated synapses without affecting neighboring ones. This raises an important question: that is, how may aspiny neurons accomplish diffusionally isolated and synapse-specific signal transduction? We propose that synapses formed by different afferents possess specific postsynaptic mechanisms for functional biochemical compartmentalization, which produce signaling microdomains with specific properties and distinct physiological roles. To determine the synapse-specific mechanisms of postsynaptic calcium compartmentalization in aspiny neurons, we will examine postsynaptic Ca2+ signals at two types of excitatory synapses of hippocampal CA1 basket cells: synapses innervated by the Schaffer collaterals and the perforant path. A combination of two-photon microscopy, electrophysiology, pharmacology, and molecular techniques will be used to assess the spatio-temporal profile of postsynaptic Ca2+ signals within different synapses as well as their regulation and physiological significance.This study will be of value to cell biologists and neuroscientists working in the fields of neurotransmission and synaptic plasticity. It is unique in that it will combine the approach of double pre- and postsynaptic fluorescent labeling in live preparations, allowing for monitoring the postsynaptic Ca2+ signal at visually identified single synapses. Such an approach sets the stage for future studies of functional biochemical compartmentalization under physiological conditions of neuronal activity.