SynCAM 1 improves survival of adult‐born neurons by accelerating synapse maturation

Abstract

The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons.

Hippocampal Neurogenesis Reduces the Dimensionality of Sparsely Coded Representations to Enhance Memory Encoding

“…This suggests that, via the same form of competition, en masse synaptic turnover could underlie learning, while only a minority of neurons actually turn over. Such a synaptic-turnover-driven neuronal turnover rule is consistent with evidence that activity-dependent competition among mature and immature DG granule cells for CA3 targets (Yasuda et al, 2011), and their input-synaptic stability (Tashiro et al, 2006; Doengi et al, 2016) appears to promote neuronal survival. Furthermore, there is a well-known overlap between factors that influence synaptic plasticity, and those that influence neurogenesis in the DG (Vivar et al, 2013), and many of these same factors influence synaptic stability more generally throughout the central nervous system (Vicario-Abejón et al, 2002).…”

“…The total number of synapses turned over in this model is greatly reduced compared to the fixed turnover model, for all coding levels (Figure 7D). Since synaptic stability is thought to determine neuronal survival in several systems (Segal, 2010), including adult-born granule cells in the DG (Doengi et al, 2016), we made a similar assumption in the model to allow us to estimate the rate of neuronal turnover. We chose the conservative assumption that a neuron dies only if all of its synapses are targeted for turnover.…”

“…Furthermore, there is a well-known overlap between factors that influence synaptic plasticity, and those that influence neurogenesis in the DG (Vivar et al, 2013), and many of these same factors influence synaptic stability more generally throughout the central nervous system (Vicario-Abejón et al, 2002). Future behavioral studies in animal models of modulated neurogenesis may benefit from measuring markers of synaptic stability, such as adhesion molecules required for synapse maintenance (Doengi et al, 2016), rather than somatic markers of neurogenesis.…”

Targeting Adult Neurogenesis to Optimize Hippocampal Circuits in Aging

“…Immature DGCs receive afferent connections in a stereotyped order [115][116][117][118], and the acquisition of these inputs is thought to govern their survival and integration into the hippocampus (Fig. 2) [118][119][120][121][122]. Adult-born DGCs be-tween~4 and 8 weeks of age exhibit heightened plasticity and are hypothesized to preferentially contribute to memory processing [118,[123][124][125][126][127][128][129][130][131][132].…”

“…Immature DGCs receive afferent connections in a stereotyped order [115][116][117][118], and the acquisition of these inputs is thought to govern their survival and integration into the hippocampus (Fig. 2) [118][119][120][121][122]. Activity of mature DGCs is thought to modulate survival of 1 to 2-week-old adult-born DGCs via hilar parvalbumin interneurons [181], whereas multiple lines of evidence suggest that~2 to 4-week-old adult-born DGCs compete with mature DGCs to receive glutamatergic perforant path inputs to integrate into the circuit [121,128] (reviewed in [113]).…”