scholarly journals Differential Effects of Lateral and Medial Entorhinal Cortex Lesions on Trace, Delay and Contextual Fear Memories

2021 ◽  
Vol 12 (1) ◽  
pp. 34
Author(s):  
Brett S. East ◽  
Lauren R. Brady ◽  
Jennifer J. Quinn

The entorhinal cortex (EC), with connections to the hippocampus, amygdala, and neocortex, is a critical, yet still underexplored, contributor to fear memory. Previous research suggests possible heterogeneity of function among its lateral (LEC) and medial (MEC) subregions. However, it is not well established what unique roles these subregions serve as the literature has shown mixed results depending on target of manipulation and type of conditioning used. Few studies have manipulated both the LEC and MEC within the same experiment. The present experiment systematically manipulated LEC and MEC function to examine their potential roles in fear memory expression. Long-Evans rats were trained using either trace or delay fear conditioning. The following day, rats received an N-methyl-D-aspartate (NMDA)-induced lesion to the LEC or MEC or received a sham surgery. Following recovery, rats were given an 8-min context test in the original context. The next day, rats were tested for tone freezing in a novel context with three discrete tone presentations. Further, rats were tested for hyperactivity in an open field under both dark and bright light gradient conditions. Results: Following either LEC or MEC lesion, freezing to context was significantly reduced in both trace and delay conditioned rats. LEC-lesioned rats consistently showed significantly less freezing following tone-offset (trace interval, or equivalent, and intertrial interval) in both trace and delay fear conditioned rats. Conclusions: These data suggest that the LEC may play a role in the expression of a conjunctive representation between the tone and context that mediates the maintenance of post-tone freezing.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Min Soo Kang ◽  
Jin-Hee Han

AbstractFormation of temporal association memory and context-specific fear memory is thought to require medial entorhinal cortex (MEC) inputs to the hippocampus during learning events. However, whether the MEC inputs are also involved in memory formation during a post-learning period has not been directly tested yet. To examine this possibility, we optogenetically inhibited axons and terminals originating from bilateral dorsal MEC excitatory neurons in the dorsal hippocampus for 5 min right after contextual fear conditioning (CFC). Mice expressing eNpHR3.0 exhibited significantly less freezing compared to control mice expressing EGFP alone during retrieval test in the conditioned context 1 day after learning. In contrast, the same optogenetic inhibition of MEC inputs performed 30 min before retrieval test did not affect freezing during retrieval test, excluding the possibility of non-specific deleterious effect of optical inhibition on retrieval process. These results support that contextual fear memory formation requires MEC inputs to the hippocampus during a post-learning period.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Caitlin S. Mallory ◽  
Kiah Hardcastle ◽  
Malcolm G. Campbell ◽  
Alexander Attinger ◽  
Isabel I. C. Low ◽  
...  

AbstractNeural circuits generate representations of the external world from multiple information streams. The navigation system provides an exceptional lens through which we may gain insights about how such computations are implemented. Neural circuits in the medial temporal lobe construct a map-like representation of space that supports navigation. This computation integrates multiple sensory cues, and, in addition, is thought to require cues related to the individual’s movement through the environment. Here, we identify multiple self-motion signals, related to the position and velocity of the head and eyes, encoded by neurons in a key node of the navigation circuitry of mice, the medial entorhinal cortex (MEC). The representation of these signals is highly integrated with other cues in individual neurons. Such information could be used to compute the allocentric location of landmarks from visual cues and to generate internal representations of space.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina F. de Veij Mestdagh ◽  
Jaap A. Timmerman ◽  
Frank Koopmans ◽  
Iryna Paliukhovich ◽  
Suzanne S. M. Miedema ◽  
...  

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.


2021 ◽  
pp. 113259
Author(s):  
Jena B. Hales ◽  
Nicole T. Reitz ◽  
Jonathan L. Vincze ◽  
Amber C. Ocampo ◽  
Stefan Leutgeb ◽  
...  

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