Abstract
Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir) conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.
Highlights
The dentate gyrus is the main gateway to the hippocampus and it constitutes a primary neurogenic niche of the adult brain
Excitatory inputs and spiking were characterized by electrophysiological recordings in GFP+ neurons and compared with those of unlabeled mature neurons of the outer granule cell layer, that are mostly generated during perinatal development (‘‘mature’’ group; see Methods section)
Injection of current steps of small amplitude readily generated action potentials in young dentate granule cells (DGCs), whereas increasingly larger currents were required to reach the membrane threshold for action potential in more mature neurons (Figure 1A–1C; Table 1). This is in agreement with previous observations that intrinsic excitability is higher in immature neurons [4,7,8,23,24,30]
Summary
The dentate gyrus is the main gateway to the hippocampus and it constitutes a primary neurogenic niche of the adult brain. Developing neurons are initially contacted by GABAergic terminals and later by glutamatergic axons. In parallel, their membrane resistance decreases and excitability becomes mature [4,7,8,9,10]. Adult-born DGCs form functional glutamatergic synapses onto dentate gyrus interneurons and CA3 pyramidal cells [13,14]. These observations indicate that new neurons receive, process and convey information onto target neurons, and might participate in hippocampal function
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