Adult hippocampal neurogenesis: are young neurons more excitable?

LUCAS MONGIAT; ALEJANDRO F. SCHINDER

San Diego, California

Congreso; Society for Neuroscience; 2007

Society for Neuroscience

The dentate gyrus (DG) of the hippocampus continues to generate new neurons throughout life. Adult-born dentate granule cells (GCs) develop and mature over several weeks, reaching a scheme of afferent connectivity and excitability that is very similar to that of neurons born during perinatal development. Thus, the adult granule cell layer contains neurons of heterogeneous ages and degrees of functional maturation, with the younger (more immature) neurons positioned at the border between the inner granule cell layer and the hilus. Young GCs have been shown to exhibit a higher input resistance and a lower threshold for the induction of long-term synaptic plasticity when compared to mature GCs. Recently, it has been proposed that young GCs might play a critical role in information processing in the adult DG. Yet, it remains unclear whether immature GCs can spike in response to an excitatory drive, which would enable them to become functionally active. In this work we aimed to define whether young GCs are capable of spiking in response to perforant path stimulation and compare their firing probability with that of mature GCs, which depends both on intrinsic neuronal excitability and strength of the entorhinal glutamatergic connections. To address this question, we labeled neural progenitor cells of the adult mouse DG using a retrovirus that carries the GFP transgene. We studied GFP+ young GCs (aging 21-29 days) in whole-cell recordings in acute brain slices and compared them with unlabeled mature GCs located at the outer granule cell layer. We monitored excitatory postsynaptic currents (EPSCs, in voltage clamp) and spiking probability (in current clamp) upon stimulation of perforant path axons at increasing strengths in the presence of GABA receptor antagonists. Young GCs exhibited significantly smaller EPSC amplitudes at all stimulus strengths, reaching plateau values of 130 ± 10 pA (young, n = 21) and 231 ± 18 pA (mature, n = 18).  When analyzed as a function of stimulus strength firing probability was similar in young and mature GCs. However, a spiking probability of 0.5 was reached with stimuli that evoked EPSC amplitudes of 90.1 ± 11.4 pA for young (n = 23) and 166 ± 19 pA for mature GCs (n = 23), highlighting the higher excitability of young neurons. We conclude that the adult hippocampus continuously generates a population of highly excitable young GCs that may play a unique role in information processing.  (Funded by the Argentine Research Council (CONICET), Agency for the Promotion of Science (ANPCyT), and Howard Hughes Medical Institute, USA)