Cellular basis of synaptic communication between
inhibitory interneurons in the hippocampus

In the hippocampus, the brain region critical for some aspects of learning and memory, particular types of GABAergic interneurons have been described to innervate exclusively other GABAergic cells (Gulyas et al., 1996). Some of these interneuron-specific interneurons (ISIs) are vulnerable in several neurological and mental conditions (e.g., epilepsy, schizophrenia, depression). However, the physiological properties, functional connectivity, and the role of ISIs in the local circuit dialogue remain undetermined.

Our aim is to investigate the functional organization of ISIs and determine their role in hippocampal computations. We currently focus on type III ISIs, which innervate GABAergic cells in the stratum oriens/alveus projecting to stratum lacunosum moleculare (O-LM) and which may control the level of inhibition received by the pyramidal neuron dendrites.

The main hypothesis is that the unique morphological and functional organization of type III ISIs allows them to efficiently integrate multiple cortical and subcortical inputs and to act as a fine-tuning device that controls the recruitment of O-LM interneurons for feedback inhibition onto distal dendrites of CA1 pyramidal neurons.

We use a combination of patch-clamp whole-cell electrophysiology and two-photon microscopy in mouse acute hippocampal slices to study:

• the physiological properties of ISIs
• input-specific synaptic integration
• the properties of inhibitory synapses made by ISIs onto their GABAergic targets
• the role of ISIs in the regulation of O-LM interneuron function and network operation

Electrophysiological and imaging experiments are supported by quantitative morphological and immunocytochemical analysis of recorded neurons.

Functional biochemical compartmentalization in aspiny dendrites
of inhibitory interneurons

Excitatory synapses of most principal neurons in the brain are made onto highly specialized cellular structures known as dendritic spines, which consist of a bulbous spine head connected to the parent dendrite through a thin spine neck. 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. This raises an important question: that is, how may aspiny neurons accomplish diffusionally isolated and synapse-specific signal transduction?

To determine the synapse-specific mechanisms regulating postsynaptic calcium compartmentalization at excitatory synapses of aspiny neurons, we examine local postsynaptic Ca2+ dynamics in distinct types of hippocampal CA1 inhibitory interneurons. We also combine simultaneous double pre- and postsynaptic fluorescent labeling in live preparations, allowing for monitoring the postsynaptic Ca2+ signal at visually identified single synapses in situ.