The hippocampus as a sorter and reverberatory integrator of sensory inputs

In entorhinal-hippocampal networks, the trisynaptic pathway, including the CA3 recurrent circuit, processes episodes of context and space. Recurrent connectivity can generate reverberatory activity, an intrinsic activity pattern of neurons that occurs after sensory inputs have ceased. However, the role of reverberatory activity in memory encoding remains incompletely understood. Here we demonstrate that in mice, synchrony between conditioned stimulus (CS) and unconditioned stimulus (US)-responsible cells occurs during the reverberatory phase, lasting for approximately 15 s, but not during CS and US inputs, in the CA1 and the reverberation is crucial for the linking of CS and US in the encoding of delay-type cued-fear memory. Retrieval-responsive cells developed primarily during the reverberatory phase. Mutant mice lacking N-methyl-D-aspartate receptors (NRs) in CA3 showed a cued-fear memory impairment and a decrease in synchronized reverberatory activities between CS- and US-responsive CA1 cells. Optogenetic CA3 silencing at the reverberatory phase during learning impaired cued-fear memory. Our findings suggest that reverberation recruits future retrieval-responsive cells via synchrony between CS- and US-responsive cells. The hippocampus uses reverberatory activity to link CS and US inputs, and avoid crosstalk during sensory inputs.

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Neurogenesis-induced forgetting is associated with reduced neuronal activity in CA1 during context fear memory retrieval

10.1101/2021.03.24.436893 ◽

2021 ◽

Author(s):

Alexandria Evans ◽

Gavin A. Scott ◽

Jonathan R. Epp

Keyword(s):

Memory Retrieval ◽

Wheel Running ◽

Fear Memory ◽

Hippocampal Neurogenesis ◽

Contextual Fear Conditioning ◽

Early Gene ◽

Population Activity ◽

Contextual Fear ◽

Induced Forgetting

AbstractHippocampal neurogenesis has a role in many essential learning and memory processes, including forgetting. This forgetting process is important because it prevents proactive interference between old and new memories. While several studies have now established the role of neurogenesis in forgetting, the specific mechanisms mediating neurogenesis-induced forgetting have not been elucidated. The goal of this study was to examine how increased neurogenesis affects the recall of context fear memory in addition to its effects on population activity within hippocampal subregions. We trained mice in contextual fear conditioning and then increased neurogenesis via 4 weeks of voluntary wheel running. Increased neurogenesis led to a reduction in freezing behaviour during context testing, replicating previous studies showing that increased neurogenesis causes forgetting of context fear memories. Additionally, we mapped the expression of the immediate early gene c-Fos within hippocampal subregions and found that increasing neurogenesis led to reduced CA1 c-Fos expression during context testing. The results suggest that reduced CA1 population activity may underlie the association between increased neurogenesis and forgetting.

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Eye Movements Actively Reinstate Spatiotemporal Mnemonic Content

Vision ◽

10.3390/vision3020021 ◽

2019 ◽

Vol 3 (2) ◽

pp. 21 ◽

Cited By ~ 13

Author(s):

Jordana S. Wynn ◽

Kelly Shen ◽

Jennifer D. Ryan

Keyword(s):

Eye Movements ◽

Memory Retrieval ◽

Memory Systems ◽

Task Demands ◽

Oculomotor Control ◽

Cognitive Resources ◽

Memory Encoding ◽

Neural Integration ◽

Spatial Locations

Eye movements support memory encoding by binding distinct elements of the visual world into coherent representations. However, the role of eye movements in memory retrieval is less clear. We propose that eye movements play a functional role in retrieval by reinstating the encoding context. By overtly shifting attention in a manner that broadly recapitulates the spatial locations and temporal order of encoded content, eye movements facilitate access to, and reactivation of, associated details. Such mnemonic gaze reinstatement may be obligatorily recruited when task demands exceed cognitive resources, as is often observed in older adults. We review research linking gaze reinstatement to retrieval, describe the neural integration between the oculomotor and memory systems, and discuss implications for models of oculomotor control, memory, and aging.

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Optogenetic scrambling of hippocampal theta oscillations alters working memory retrieval but not hippocampal spatiotemporal codes

10.1101/2021.12.24.474139 ◽

2021 ◽

Author(s):

Guillaume Etter ◽

Suzanne van der Veldt ◽

Jisoo Choi ◽

Sylvain Williams

Keyword(s):

Working Memory ◽

Memory Retrieval ◽

Recognition Task ◽

Medial Septum ◽

Inhibitory Neurons ◽

Memory Encoding ◽

Exact Role ◽

Match To Sample ◽

Hippocampal Theta

The precise temporal coordination of activity in the brain is thought to be fundamental for memory encoding and retrieval. The medial septum (MS) provides the largest source of innervation to the hippocampus (HPC), and its inhibitory neurons play a major role in controlling HPC theta (~8 Hz) oscillations. While pharmacological inhibition of the MS is associated with memory impairment, the exact role of MS inhibitory neurons in HPC function and memory is not fully understood. While HPC place cells were previously reported to not depend on MS inputs, the exact role of MS inputs on HPC temporal codes is still a matter of debate. Moreover, pharmacological manipulations do not have the temporal resolution to distinguish the role of MS activity on working memory encoding, retention and retrieval. Here we stimulated the MS with optogenetics to either pace or ablate theta, while recording large hippocampal assemblies over time using calcium imaging along with local field potentials to monitor theta control. Using scrambled light stimulation, we could robustly ablate theta signals, which was associated with direct modulation of a subpopulation of neurons in the HPC. We found that such stimulation led to decreased working memory retrieval, but not encoding in both a delayed non-match to sample task and a novel place object recognition task. Strikingly, scrambled stimulations were not associated with disrupted spatiotemporal codes. Importantly, we show that our opsin did not transfect cholinergic cells and stimulation did not disrupt HPC ripple activity or running speed, suggesting a specific role for MS GABAergic cells in memory maintenance and retrieval that is independent from these other potential confounding mechanisms. Our study suggests that theta signals play a specific and essential role in supporting working memory retrieval and maintenance while not being necessary for hippocampal spatiotemporal codes.

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Eye Movements Actively Reinstate Spatiotemporal Mnemonic Content

10.20944/preprints201905.0132.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jordana Wynn ◽

Kelly Shen ◽

Jennifer Ryan

Keyword(s):

Eye Movements ◽

Memory Retrieval ◽

Memory Systems ◽

Task Demands ◽

Oculomotor Control ◽

Cognitive Resources ◽

Memory Encoding ◽

Neural Integration ◽

Spatial Locations

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Supramammillary nucleus synchronizes with dentate gyrus to regulate spatial memory retrieval through glutamate release

eLife ◽

10.7554/elife.53129 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Yadong Li ◽

Hechen Bao ◽

Yanjia Luo ◽

Cherasse Yoan ◽

Heather Anne Sullivan ◽

...

Keyword(s):

Spatial Memory ◽

Dentate Gyrus ◽

Memory Retrieval ◽

Glutamate Release ◽

Relative Role ◽

Memory Encoding ◽

Supramammillary Nucleus ◽

Subcortical Regions ◽

Highly Correlated

The supramammillary nucleus (SuM) provides substantial innervation to the dentate gyrus (DG). It remains unknown how the SuM and DG coordinate their activities at the circuit level to regulate spatial memory. Additionally, SuM co-releases GABA and glutamate to the DG, but the relative role of GABA versus glutamate in regulating spatial memory remains unknown. Here we report that SuM-DG Ca2+ activities are highly correlated during spatial memory retrieval as compared to the moderate correlation during memory encoding when mice are performing a location discrimination task. Supporting this evidence, we demonstrate that the activity of SuM neurons or SuM-DG projections is required for spatial memory retrieval. Furthermore, we show that SuM glutamate transmission is necessary for both spatial memory retrieval and highly-correlated SuM-DG activities during spatial memory retrieval. Our studies identify a long-range SuM-DG circuit linking two highly correlated subcortical regions to regulate spatial memory retrieval through SuM glutamate release.

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