Alberto Bacci’s team aims at gaining more detailed information on the properties of neocortical interneurons, using a combination of electrophysiological, cellular, biochemical and morphological techniques. The ultimate goal of his research is to understand the functional relevance of these different neuron subtypes within cortical circuits.
The importance of inhibition
In the mammalian brain, the neocortex is the site where sensory information is integrated into complex cognitive functions. This is accomplished by the activity of both principal glutamatergic neurons and locally-projecting inhibitory GABAergic interneurons, interconnected in complex networks. Inhibitory neurons play several key roles in neocortical function. For example, they shape sensory receptive fields and drive several high frequency network oscillations. On the other hand, defects in their function can lead to devastating diseases, such as epilepsy and schizophrenia.
Alberto has examined properties of two major functional interneuron subclasses in neocortical layer V: fast-spiking (FS) basket cells and low-threshold spiking (LTS) interneurons. His previous data indicate that each group expresses a novel form of self-inhibition, namely autaptic inhibitory transmission in FS cells and an endocannabinoid-mediated slow self-inhibition in LTS interneurons. Moreover, he recently found that endocannabinoid self-modulation occurs in a population of pyramidal glutamatergic neurons of layer 2/3.
Building blocks of diversity
Important clues to understand the functional role of each interneuron subtype within cortical microcircuits can be obtained by the study of the development of the building blocks of cortical networks: the synaptic connections originating from different subtypes of interneurons onto principal cortical neurons, such as large layer V pyramidal neurons. These neurons are prominent output elements of the neocortex and their activity influences several subcortical areas in the central nervous system. It has been shown that different interneuron subtypes make synapses onto different compartments of pyramidal neurons therefore controlling their input-output characteristics. Interestingly, synapses made onto pyramidal neurons by different interneuron subtypes, targeting pyramidal-neuron soma (e.g. basket cells) or dendrites (e.g. Martinotti cells) are characterized by expression of specific subunits of GABAA receptors.
The far-west of fast-spiking cells
The self-inhibiting properties of FS cells and LTS interneurons open several crucial questions:
1) What is the role of FS cell autapses in coordinating fast network synchrony?
2) What are the molecular mechanisms underlying autaptic asynchronous release, prolonging FS cell self-inhibition by several seconds, and what is its relevance during physiological and pathological network activities?
3) What are the induction mechanisms, the molecular players involved and the functional roles within cortical microcircuits of the endocannabinoid-mediated long-lasting self-inhibition in LTS interneurons and pyramidal neurons?
Alberto Bacci joined the ICM in 2011, with him team Cellular physiology of cortical microcircuits. He received a M.Sc. in 1994 and a Ph.D. in experimental pharmacology and therapeuthics from University of Milano in 2000,and did postdoctoral work at the Department of Neurology of Stanford University. He is recipient of several awards and his research has been and is currently supported by the ERC, Giovanni Armenise-Harvard Foundation, NARSAD.