Norepinephrine as a spatial memory reset signal

Abstract

Contextual information is represented in the hippocampus (HPC) partially through the recruitment of distinct neuronal ensembles. It is believed that reactivation of these ensembles underlies memory retrieval processes. Recently, we showed that norepinephrine input from phasic locus coeruleus activation induces hippocampal plasticity resulting in the recruitment of new neurons and disengagement from previously established representations. We hypothesize that norepinephrine may provide a neuromodulatory mnemonic switch signaling the HPC to move from a state of retrieval to encoding in the presence of novelty, and therefore, plays a role in memory updating. Here, we tested whether bilateral dorsal dentate gyrus (dDG) infusions of the β-adrenergic receptor (BAR) agonist isoproterenol (ISO), administered prior to encoding or retrieval, would impair spatial working and reference memory by reverting, the system to encoding (thereby recruiting new neurons) potentially interfering with the retrieval of the previously established spatial ensemble. We also investigated whether dDG infusions of ISO could promote cognitive flexibility by switching the system to encoding when it is adaptive (ie, when new information is presented, eg, reversal learning). We found that intra-dDG infusions of ISO given prior to retrieval caused deficits in working and reference memory which was blocked by pretreatment with the BAR-antagonist, propranolol (PRO). In contrast, ISO administered prior to reversal learning led to improved performance. These data support our hypothesis that norepinephrine serves as a novelty signal to update HPC contextual representations via BAR activation-facilitated recruitment of new neurons. This can be both maladaptive and adaptive depending on the situation. Behavioural

Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear

“…We speculate that the efficacy of our stimulation may be disrupted when it occurs later in the session as the mice are taken out of the chamber as soon as stimulation ends. We believe that this type of stimulation may promote new learning 70 (e.g., extinction) and since the mice were left in the chamber for an additional ten minutes in the F10 condition, the context could theoretically serve as a substrate for learning, especially given that conditioned fear decreases across the session. However, it is also possible that since mice were shocked within the interval of 198–440 s during fear-conditioning the prior day, that the memory was more malleable early in the recall session as this is when the highest degree of shock expectation would theoretically occur.…”

Contextual memory engrams, and the neuromodulatory influence of the locus coeruleus

“…In this context, we investigate the role of catecholamines, specifically norepinephrine (NE) and dopamine (DA), in hippocampal-dependent memory. Our exploration aims to elucidate a potentially significant pathway for memory updating, highlighting the involvement of NE/DA projections from the locus coeruleus (LC) to the hippocampus in the remapping and sculpting of contextual representations (Grella et al, 2019(Grella et al, , 2021.…”

The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

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