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Alberto Bacci"Self-inhibiting neurons in the neocortex"

Abstract :


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. Cortical interneurons represent a highly heterogeneous cell population.
Understanding the specific role of each interneuron subtype within cortical microcircuits is still a crucial open question. We have examined properties of two major functional interneuron subclasses in neocortical layer V: fast-spiking (FS) and low-threshold spiking
(LTS) cells. Our 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. Autaptic transmission has a very high incidence in FS interneurons (~85%) and generates very large responses, providing functional self-inhibition. GABAergic autapses are instrumental in enhancing FS-cell spike timing precision with important consequences in network oscillation generation.
On the other hand, LTS interneurons lack functional GABAergic autaptic transmission. However, in response to their own repetitive AP discharges, they generate a hyperpolarizing slow self-inhibition
(SSI) that is large (up to 10 mV) and long-lasting (>30 min), and elicited by autocrine release of endocannabinoids (ECs) resulting in the opening of K+ channels. Pharmacological evidence indicated that LTS-cell SSI appears to be mediated by the endocannabinoid 2-AG.
Finally, recent preliminary data suggest that this endocannabinoid-mediated depression of cell excitability might occur also in a subpopulation of cortical glutamatergic neurons.

Selected publications

Bacci A., Huguenard JR. (2006) Enhancement of spike timing precision by autaptic transmission in neocortical inhibitory interneurons. Neuron 49:119-30.
Bacci A., Huguenard JR, Prince DA. (2005) Modulation of neocortical interneurons: extrinsic influences and exercises in self-control. Trends in Neurosci. 28:602-611.
Bacci A., Huguenard JR, Prince DA. (2004) Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431:312-316.
Bacci A., Rudolph U, Huguenard JR, Prince DA. (2003) Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses. J. Neurosci. 23:9664-9674.

Giovanni Marsicano