A shift in the mechanisms controlling hippocampal engram formation during brain maturation

Abstract

The ability to form precise, episodic memories develops with age, with young children only able to form gist-like memories that lack precision. The cellular and molecular events in the developing hippocampus that underlie the emergence of precise, episodic-like memory are unclear. In mice, the absence of a competitive neuronal engram allocation process in the immature hippocampus precluded the formation of sparse engrams and precise memories until the fourth postnatal week, when inhibitory circuits in the hippocampus mature. This age-dependent shift in precision of episodic-like memories involved the functional maturation of parvalbumin-expressing interneurons in subfield CA1 through assembly of extracellular perineuronal nets, which is necessary and sufficient for the onset of competitive neuronal allocation, sparse engram formation, and memory precision.

Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation

“…Second, to reveal stress-induced changes in neural excitability we collected brain tissue 90 minutes after conditioning paradigm ( Figure 2H ), and carried out immunostaining for c-Fos in the lateral amygdala ( Figures 2I,J , and S1E,F ). We report a significant increase in c-Fos density following fear acquisition in the ELS group, consistent with other reports of memory generalisation and c-Fos density, with c-Fos density inversely correlated with memory accuracy (38).…”

“…One interpretation of these data is that astrocytes might tune engram formation, with astrocyte dysfunction increasing c-Fos expression resulting in a loss of specificity of the memory trace and generalisation of fear. Evidence of this mechanism whereby increased c-Fos levels inversely correlate with memory accuracy have been recently shown in hippocampal circuits (38). In addition, astrocyte-engram neuron interactions have recently been identified (45) suggesting a potential participation of astrocytes in engram stabilisation.…”

“…shown in hippocampal circuits (38). In addition, astrocyte-engram neuron interactions have recently been identified (45) suggesting a potential participation of astrocytes in engram stabilisation.…”

Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation

“…PTN (pleiotrophin) and its receptor PTPRZ1 are associated with increased DG neurogenesis in a mouse model of senescence following exposure to environmental enrichment 75,76 . HALPN1 (hyaluronan and proteoglycan link protein 1) is important for maturation of perineuronal nets in the mouse dorsal CA1 that surround PV+ interneurons, which affects neuronal allocation and memory precision 77 . Periostin (POSTN) promotes neural stem cell proliferation as well as neuronal and astroglial in vitro, while periostin injection into the lateral ventricles of neonatal rats after hypoxic-ischemic brain injury stimulates proliferation and differentiation in the SGZ 55 .…”

Parallel maturation of hippocampal memory and CA1 task representations

“…The ability to integrate diverse cues may be cri�cal to the ability to form detailed and specific memories -a hallmark of hippocampal memory. As such, we sought to inves�gate the development of non-spa�al encoding in hippocampal place cells.To this end, we recorded from popula�ons of CA1 place cells in P17-P28 rat pups -the developmental period when adult-like hippocampal memory emerges in rats [8][9][10]16 -while the pups carried out a hippocampal-dependent memory task that requires animals to alternate between sample and memory-guided task phases (discrete trial, delayed non-matching to place (DNMP) 17,18 ). In adult animals, this task is associated with a strong influence of non-spa�al features of the task on CA1 place cell ac�vity -place cells display robust remapping between the two phases of the task 15 .…”