Varsavsky, Isabella; (2024) The emergence of neural mechanisms for memory specificity during post-natal development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Episodic memory, the ability to recall specific events, emerges late in human development. Prior to this, individuals experience "infantile generalization," characterized by imprecise memory recall and an inability to accurately place events within a temporal and spatial context. The prevailing hypothesis attributes this phenomenon to a developmental imbalance between pattern separation (PS) and pattern completion (PC), neural mechanisms for differentiating memories from similar neural representations and reconstructing memories from partial sensory cues, respectively. In development, PS emerges late leading to a reliance on generalization over specificity. Research in adult rats indicates that these processes predominantly occur in the dentate gyrus (DG) and CA3 regions of the hippocampus. Thus, the developmental immaturity of these regions, particularly the unusually late maturation granule cells of the DG, might contribute to infantile generalization. In the past, it has been a challenge to distinguish between the two main excitatory cell types of the DG (granule and mossy cells) using in in vivo electrophysiology. However, we address this issue by adapting recently published protocols to the developing DG-CA3 circuit (Goodsmith et al., 2019; Senzai and Buszaki, 2017). This thesis provides the first electrophysiological characterization of DG and CA3 cells in the postnatal rat. In addition, we evaluated the PS ability of these cells by exposing rats to spatial contexts with similar or distinct elements during ages corresponding to the onset of episodic memory (P16-P32). We found evidence of PC in CA3 throughout the age window. Notably, there was no evidence of PS in granule cells, suggesting that their protracted maturation may not be the primary factor behind infantile generalization. In contrast, mossy cells developed PS after weaning implying this ability functions through distinct mechanisms in the two cell types and underscoring the significance of mossy cells in the emergence of memory specificity during the postnatal period in rats.

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