Biology subjects

Sheffield, M. E. J.

Publications and source records attributed to Sheffield, M. E. J..

3 recordsLinked to original sources

bioRxiv2023

Reward Expectation Reduces Representational Drift in the Hippocampus

Spatial memory in the hippocampus involves dynamic neural patterns that change over days, termed representational drift. While drift may aid memory updating, excessive drift could impede retrieval. Memory retrieval is influenced by reward expectation during encoding, so we hypothesized that diminished reward expectation would exacerbate representational drift. We found that high reward expectation limited drift, with CA1 representations on one day gradually re-emerging over successive trials the following day. Conversely, the absence of reward expectation resulted in increased drift, as the gradual re-emergence of the previous days representation did not occur. At the single cell level, lowering reward expectation caused an immediate increase in the proportion of place-fields with low trial-to-trial reliability. These place fields were less likely to be reinstated the following day, underlying increased drift in this condition. In conclusion, heightened reward expectation improves memory encoding and retrieval by maintaining reliable place fields that are gradually reinstated across days, thereby minimizing representational drift.

neuroscience↗

bioRxiv2023

Distinct catecholaminergic pathways projecting to hippocampal CA1 transmit contrasting signals during behavior and learning

Neuromodulatory inputs to the hippocampus play pivotal roles in modulating synaptic plasticity, shaping neuronal activity, and influencing learning and memory. Recently it has been shown that the main sources of catecholamines to the hippocampus, ventral tegmental area (VTA) and locus coeruleus (LC), may have overlapping release of neurotransmitters and effects on the hippocampus. Therefore, to dissect the impacts of both VTA and LC circuits on hippocampal function, a thorough examination of how these pathways might differentially operate during behavior and learning is necessary. We therefore utilized 2-photon microscopy to functionally image the activity of VTA and LC axons within the CA1 region of the dorsal hippocampus in head-fixed male mice navigating linear paths within virtual reality (VR) environments. We found that within familiar environments some VTA axons and the vast majority of LC axons showed a correlation with the animals running speed. However, as mice approached previously learned rewarded locations, a large majority of VTA axons exhibited a gradual ramping-up of activity, peaking at the reward location. In contrast, LC axons displayed a pre-movement signal predictive of the animals transition from immobility to movement. Interestingly, a marked divergence emerged following a switch from the familiar to novel VR environments. Many LC axons showed large increases in activity that remained elevated for over a minute, while the previously observed VTA axon ramping-to-reward dynamics disappeared during the same period. In conclusion, these findings highlight distinct roles of VTA and LC catecholaminergic inputs in the dorsal CA1 hippocampal region. These inputs encode unique information, with reward information in VTA inputs and novelty and kinematic information in LC inputs, likely contributing to differential modulation of hippocampal activity during behavior and learning.

neuroscience↗

bioRxiv2023

Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval

Memory retrieval of fearful experiences is essential for survival but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual fear extinction and strongly projects to hippocampal subregion CA1. However, the NR-CA1 pathway has not been investigated during behavior, leaving unknown its role in contextual fear memory retrieval. We implement a novel head-restrained virtual reality CFC paradigm and show that inactivation of the NR-CA1 pathway prolongs fearful freezing epochs, induces fear generalization, and delays extinction. We use in vivo sub-cellular imaging to specifically record NR-axons innervating CA1 before and after CFC. We find NR-axons become selectively tuned to freezing only after CFC, and this activity is well-predicted by an encoding model. We conclude that the NR-CA1 pathway actively suppresses fear responses by disrupting ongoing hippocampal-dependent contextual fear memory retrieval.

neuroscience↗