Immature dentate granule cells require Ntrk2/TrkB for the formation of functional hippocampal circuitry
A study recently published in iScience journal (Cell Press) by Enrico Cherubini e Marilena Griguoli’s group (EBRI Laboratory - Cortical microcircuits and neurodevelopmental disorders) in collaboration with Liliana Minichiello (Oxford University), has unveiled that, early in the postnatal period, the selective removal of TrkB from dentate gyrus granule cells (involved in learning and memory processes) during a critical window when these cells integrate the classic trisynaptic circuit, causes in targeted neurons a premature shift of GABA from the depolarizing and excitatory (as immediately after birth) to the hyperpolarizing direction. This action of GABA, due to a down regulation of the cation-chloride importer NKCC1, induces structural changes associated with alterations in network activity such as giant depolarizing potentials with consequent impairment of synaptic plasticity and memory in adulthood.
These results demonstrate that BDNF, via activation of TrkB receptors and in synergy with the depolarizing action of GABA, play a key role in the development of neuronal hippocampal circuits. An impairment of these mechanisms early in postnatal development leads to cognitive deficits as observed in Neurodevelopmental Disorders.