Neurogenesis mediated plasticity is associated with reduced neuronal activity in CA1 during context fear memory retrieval

Abstract

Postnatal hippocampal neurogenesis has been demonstrated to affect learning and memory in numerous ways. Several studies have now demonstrated that increased neurogenesis can induce forgetting of memories acquired prior to the manipulation of neurogenesis and, as a result of this forgetting can also facilitate new learning. However, the mechanisms mediating neurogenesis-induced forgetting are not well understood. Here, we used a subregion-based analysis of the immediate early gene c-Fos as well as in vivo fiber photometry to determine changes in activity corresponding with neurogenesis induced forgetting. We found that increasing neurogenesis led to reduced CA1 activity during context memory retrieval. We also demonstrate here that perineuronal net expression in areas CA1 is bidirectionally altered by the levels or activity of postnatally generated neurons in the dentate gyrus. These results suggest that neurogenesis may induce forgetting by disrupting perineuronal nets in CA1 which may otherwise protect memories from degradation.

Elimination of perineuronal nets in CA1 disrupts GABA release and long‐term contextual fear memory retention

“…In fact, dynamic regulation of PNNs expression in the adult auditory cortex is vital for fear learning and consolidation in response to pure tones (Banerjee et al, 2017). PNNs expression in the CA1 hippocampus is bidirectionally regulated by the activity of postnatally generated neurons in the dentate gyrus (Evans et al, 2022). Lack of PNNs cause the changed inhibition in several studies, but the conclusion is inconsistent.…”

Sharpening the blades of the dentate gyrus: how adult‐born neurons differentially modulate diverse aspects of hippocampal learning and memory

“…Extending the same concept to neurogenesis, a genetic manipulation increasing newborn neurons similarly enhanced feed-forward inhibition and increased the inhibitory tone of CA3 and CA1 parvalbumin interneurons (Berdugo-Vega et al, 2020). Given that CA1 parvalbumin cells are not directly innervated by newborn neurons, this suggests an overall attenuation of hippocampal activity upon increased neurogenesis that has also been linked to forgetting (Evans et al, 2022). Importantly, enhancing neurogenesis also had consequences in the profile of sharp-wave ripples in CA1 (Berdugo-Vega et al, 2020), which are important patterns of activity associated with memory consolidation (Buzs aki, 2015).…”

Hypocretin/orexin neurons encode social discrimination and exhibit a sex-dependent necessity for social interaction

“…Data from the Ca 2+ -dependent 465 nm channel were then linearly scaled using the fitted decay of the isosbestic channel, correcting for any photobleaching which occurred during the recordings (Meng et al, 2018). The resulting vector was converted to a ΔF/F trace as previously described (Evans et al, 2022), and each trace was normalized as a z-score (Reichenbach et al, 2022). Z-scored ΔF/F traces were analyzed for area under the curve, peak frequency, and maximum fluorescence.…”

“…Comparisons of AUC during specific behaviours were normalized by the summed duration of the behavioural epochs of interest. Peak frequency was refined using a peak detection filter of 2 standard deviations above the median z-scored ΔF/F value of the recording session (Evans et al, 2022; Moda-Sava et al, 2019). For all behaviour-specific analyses, photometry and behavioural timeseries vectors were aligned using nearest-neighbours approximation to account for differences in framerates across recording modalities.…”