Basal Forebrain Cholinergic Neurons Have Specific Characteristics during the Perinatal Period.

Cholinergic neurons of the basal forebrain represent the main source of cholinergic innervation of large parts of the neocortex and are involved in adults in the modulation of attention, memory, and arousal. During the first postnatal days, they play a crucial role in the development of cortical neurons and cortical cytoarchitecture. However, their characteristics, during this period have not been studied.

The early excitatory action of striatal cholinergic-GABAergic microcircuits conditions the subsequent GABA inhibitory shift.

Cholinergic interneurons of the striatum play a role in action selection and associative learning by activating local GABAergic inhibitory microcircuits. We investigated whether cholinergic-GABAergic microcircuits function differently and fulfill a different role during early postnatal development, when GABA actions are not inhibitory and mice pups do not walk. We focused our study mainly on dual cholinergic/GABAergic interneurons (CGINs).

Enhanced Glutamatergic Currents at Birth in Shank3 KO Mice.

Autism spectrum disorders (ASD) are neurodevelopmental disorders induced by genetic and environmental factors. In our recent studies, we showed that the GABA developmental shifts during delivery and the second postnatal week are abolished in two rodent models of ASD. Maternal treatment around birth with bumetanide restored the GABA developmental sequence and attenuated the autism pathogenesis in offspring.

Early alterations in a mouse model of Rett syndrome: the GABA developmental shift is abolished at birth.

Genetic mutations of the Methyl-CpG-binding protein-2 (MECP2) gene underlie Rett syndrome (RTT). Developmental processes are often considered to be irrelevant in RTT pathogenesis but neuronal activity at birth has not been recorded. We report that the GABA developmental shift at birth is abolished in CA3 pyramidal neurons of Mecp2 mice and the glutamatergic/GABAergic postsynaptic currents (PSCs) ratio is increased.

Striatal dual cholinergic /GABAergic transmission in Parkinson disease: friends or foes?

The rule of one terminal and one transmitter acting on one synapse clearly fails to cover the complexity of chemical synapse operation in the brain. Compelling evidence now indicates that two transmitters can be released from the same terminal, acting in a complementary manner to generate complex electrical activity in the targets. Our laboratory now showed that a subpopulation striatal cholinergic neurons also release the classical inhibitory transmitter GABA with a balance between excitation and inhibition being provided by acetylcholine and GABA, respectively.