Cellular Physiology of Cortical Microcircuits

Pyramidal neurons (Bacci) (ori)
Pyramidal neurons in the neocortex of a genetically modified mouse, engineered to express a fluorescent protein selectively in projecting principal neurons.

Interneuron (Bacci) (ori)
Infrared image of an interneuron (above) and its electrical activity (under).

Interneuron e- activity (Bacci) (ori)

In the mammalian brain, the neocortex is the final destination and site of storage and processing of all sensory information. The anatomical organization of the neocortex is stereotypical among different species and consists of six layers in which specific subtypes of excitatory and inhibitory neurons generate complex intertwined networks, whose rhythmic activities are responsible for complex behavioral functions, such as cognition, movement initiation and memory.

The major interest of our laboratory is the study of the cellular physiology of various elements of cortical microcircuits, the properties of their connections and their contribution to various network activities. Cortical neurons represent one of the most heterogeneous cell population in the central nervous system. The ultimate goal of our research is to understand the functional relevance of these different neuron subtypes within cortical circuits.

In particular, our laboratory focuses on locally projecting inhibitory GABAergic neurons (interneurons), whose activity is crucial, as they represent the basic elements that provide cortical feedforward and feedback inhibition and prevent development of epilepsy. Moreover, neocortical inhibitory interneurons generate, pace and modulate the oscillatory activity of large neuronal populations.

We have previously identified that fast spiking (FS) and low-threshold spiking (LTS) interneurons in neocortical layer V are controlled by distinct self-inhibitory mechanisms, each unique and powerful. FS cells form functional GABAergic autaptic contacts, which, once activated by their own action potentials, generate a fast, precise and transient inhibition. In contrast, LTS cells, in response to their own repetitive discharges, generate a hyperpolarizing slow self-inhibition (SSI) that is large and long-lasting and likely results from autocrine action of endocannabinoids.

Using a combination of electrophysiological, cellular, biochemical and morphological techniques, we aim at gaining more detailed information on properties of neocortical interneurons, with a focus on mechanisms and functions of these two forms of self-modulation.