Role of NMDA receptors in adult neurogenesis: an ontogenetic (re)view on activity-dependent development

Abstract

It is now widely accepted that neurogenesis continues throughout life. Accumulating evidence suggests that neurotransmitters are essential signaling molecules that control the different steps of neurogenesis. Nevertheless, we are only beginning to understand the precise role of neurotransmitter receptors and in particular excitatory glutamatergic transmission in the differentiation of adult-born neurons. Recent technical advances allow single-cell gene deletion to study cell-autonomous effects during the maturation of adult-born neurons. Single-cell gene deletion overcomes some of the difficulties in interpreting global gene deletion effects on entire brain areas or systemic pharmacological approaches that might result in compensatory circuit effects. The aim of this review is to summarize recent advances in the understanding of the role of NMDA receptors (NMDARs) during the differentiation of adult-born neurons and put them in perspective with previous findings on cortical development.

Functional properties of extrasynaptic AMPA and NMDA receptors during postnatal hippocampal neurogenesis

“…They might help to modulate proliferation and shift determination of daughter cells towards neuronal fate in an activity‐dependent manner (Deisseroth et al 2004). Furthermore, it was also reported that neuronal progenitors and neuroblasts continue to express ionotropic glutamate receptors which were suggested to restrict migration and regulate positioning of newborn neurons dependent on glutamate spillover from neighbouring synapses (Namba et al 2011; Platel & Kelsch, 2013). Therefore, it is not surprising that the postmitotic newborn granule cells express functional extrasynaptic ionotropic glutamate receptors even before synaptic integration.…”

Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis

“…1b), with nonsynaptic, ambient GABA as the first input and synaptic glutamate from Ent as the last 33,35,83 . Taken together with the fact that new neurons have a lower threshold for firing relative to embryonic-generated neurons and that they are sensitive to activity-dependent regulation 36,85–87 , the emerging view is that immature adult-generated DG neurons are distinct from mature adult-generated and all embryonic-generated DG neurons in that they are “young and excitable” 88 , function independently of inhibitory GABA circuits 89 and receive direct innervation from their glutamatergic “elders” 84 . In fact, some work suggests that adult-generated neurons remain functionally distinct from their embryonic-generated counterparts 90 .…”

Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain

“…These neurons become granule cells (GCs), the principal neurons in the dentate gyrus (DG) of the hippocampus, and they functionally integrate into the hippocampal circuitry ( van Praag et al, 2002 ; Toni et al, 2008 ). This extreme form of structural remodeling, similar to many other forms of experience-dependent plasticity, requires activation of NMDA receptors (NMDARs) ( Platel and Kelsch, 2013 ). Blockade of NMDARs rapidly increases the proliferation of neural precursor cells, whereas stimulation of NMDARs promotes neuronal fate specification ( Cameron et al, 1995 ; Deisseroth et al, 2004 ).…”