Effects of adult‐generated granule cells on coordinated network activity in the dentate gyrus

Abstract

Throughout the adult life of most mammals, new neurons are continuously generated in the dentate gyrus of the hippocampal formation. Recent work has documented specific cognitive deficits after elimination of adult hippocampal neurogenesis in rodents, suggesting that these neurons may contribute to information processing in hippocampal circuits. Young adult-born neurons exhibit enhanced excitability and have altered capacity for synaptic plasticity in hippocampal slice preparations in vitro. Still, little is known about the effect of adult-born granule cells on hippocampal activity in vivo. In order to assess the impact of these new neurons on neural circuits in the dentate, we recorded perforant-path evoked responses and spontaneous network activity from the dentate gyrus of urethane-anesthetized mice whose hippocampus had been focally X-irradiated to eliminate the population of young adult-born granule cells. After X-irradiation, perforant-path responses were reduced in magnitude. In contrast, there was a marked increase in the amplitude of spontaneous gamma-frequency bursts in the dentate gyrus and hilus, as well as increased synchronization of dentate neuron firing to these bursts. A similar increase in gamma burst amplitude was also found in animals in which adult neurogenesis was eliminated using the GFAP:TK pharmacogenetic ablation technique. These data suggest that young neurons may inhibit or destabilize recurrent network activity in the dentate and hilus. This unexpected result yields a new perspective on how a modest number of young adult–generated granule cells may modulate activity in the larger population of mature granule cells, rather than acting solely as independent encoding units.

Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

“…g frequency oscillations are predominately mediated by the coherent firing of parvalbumin-expressing basket cells (Gulyás et al 2010). Hence, these findings strongly implicate abGCs in the local control of IN activity that feeds back onto the entire GC population to control firing (Lacefield et al 2012). Such observations are consistent with the morphology of DG PV basket cells that receive input from GCs and extend axonal arborizations across large swathes of the GCL (Lübke et al 1998) and support the hypothesis that abGCs impact activity across the entire DG network (see also Piatti et al 2013).…”

“…We are particularly interested in this facet of neurogenesis and believe that a theory of abGC function will not be complete without consideration of each cell's numerous synaptic partners rather than just its EC inputs and its output to CA3 pyramidal neurons (Sahay et al 2011a). Lacefield et al (2012) provided, to date, the only in vivo data exploring the impact of abGCs on DG network activity. This study focused on spontaneously occurring g bursts in the DG of anesthetized mice that lacked abGCs.…”

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…Recently, adultborn neurons have been shown to inhibit the cellular activity of "mature" granule neurons. Indeed, depleting neurogenesis increases the spontaneous g network activity (Lacefield et al 2010). In contrast, increasing adult neurogenesis reduces the spread of activity and strength of neuronal activation in the DG (Ikrar et al 2013).…”

Functional Differentiation of Adult-Born Neurons along the Septotemporal Axis of the Dentate Gyrus: Figure 1.

“…Alternately, it may be that adult-born neurons do not themselves mediate distinct tasks, but effect differential behaviors by nature of altering the local network circuitry Lacefield et al 2012), which is itself functionally dissociated. To wit, recent work has shown an interaction between depressive-like state and performance on neurogenesis-dependent memory tests (Dery et al 2013;Shelton and Kirwan 2013), indicating that the contribution of adult hippocampal neurogenesis to depression and anxiety disorders may, in fact, be because of deficits in correct emotional responses to appropriate contextual stimuli (Becker and Wojtowicz 2007;Kheirbek et al 2012).…”