scholarly journals Entorhinal cortical Island cells regulate temporal association learning with long trace period

2021 ◽  
Vol 28 (9) ◽  
pp. 319-328
Author(s):  
Jun Yokose ◽  
William D. Marks ◽  
Naoki Yamamoto ◽  
Sachie K. Ogawa ◽  
Takashi Kitamura
Keyword(s):  
Fear Conditioning ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Temporal Association ◽  
Association Learning ◽  
Trace Fear Conditioning ◽  
Dorsal Hippocampal ◽  
Neural Input ◽  
Hippocampal Ca1 ◽  
Trace Fear

Temporal association learning (TAL) allows for the linkage of distinct, nonsynchronous events across a period of time. This function is driven by neural interactions in the entorhinal cortical–hippocampal network, especially the neural input from the pyramidal cells in layer III of medial entorhinal cortex (MECIII) to hippocampal CA1 is crucial for TAL. Successful TAL depends on the strength of event stimuli and the duration of the temporal gap between events. Whereas it has been demonstrated that the neural input from pyramidal cells in layer II of MEC, referred to as Island cells, to inhibitory neurons in dorsal hippocampal CA1 controls TAL when the strength of event stimuli is weak, it remains unknown whether Island cells regulate TAL with long trace periods as well. To understand the role of Island cells in regulating the duration of the learnable trace period in TAL, we used Pavlovian trace fear conditioning (TFC) with a 60-sec long trace period (long trace fear conditioning [L-TFC]) coupled with optogenetic and chemogenetic neural activity manipulations as well as cell type-specific neural ablation. We found that ablation of Island cells in MECII partially increases L-TFC performance. Chemogenetic manipulation of Island cells causes differential effectiveness in Island cell activity and leads to a circuit imbalance that disrupts L-TFC. However, optogenetic terminal inhibition of Island cell input to dorsal hippocampal CA1 during the temporal association period allows for long trace intervals to be learned in TFC. These results demonstrate that Island cells have a critical role in regulating the duration of time bridgeable between associated events in TAL.

scholarly journals Hippocampal network reorganization underlies the formation of a temporal association memory

2019 ◽  
Author(s):  
Mohsin S. Ahmed ◽  
James B. Priestley ◽  
Angel Castro ◽  
Fabio Stefanini ◽  
Elizabeth M. Balough ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Time Course ◽  
Neural Population ◽  
Temporal Association ◽  
Persistent Activity ◽  
Population Activity ◽  
Association Learning ◽  
Trace Fear Conditioning ◽  
Hippocampal Network ◽  
Trace Fear

AbstractEpisodic memory requires linking events in time, a function dependent on the hippocampus. In “trace” fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use 2-photon calcium imaging to track neural population dynamics over the complete time-course of learning and show that, in contrast to previous theories, the hippocampus does not generate persistent activity to bridge the time delay. Instead, learning is concomitant with broad changes in the active neural population in CA1. While neural responses were highly stochastic in time, cue identity could be reliably read out from population activity rates over longer timescales after learning. These results question the ubiquity of neural sequences during temporal association learning, and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.

Trace fear conditioning enhances synaptic and intrinsic plasticity in rat hippocampus

2012 ◽  
Vol 107 (12) ◽  
pp. 3397-3408 ◽  
Author(s):  
Chenghui Song ◽  
Julia A. Detert ◽  
Megha Sehgal ◽  
James R. Moyer
Keyword(s):  
Fear Conditioning ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Physiological Data ◽  
Trace Fear Conditioning ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Trace Fear ◽  
Intrinsic Plasticity

Experience-dependent synaptic and intrinsic plasticity are thought to be important substrates for learning-related changes in behavior. The present study combined trace fear conditioning with both extracellular and intracellular hippocampal recordings to study learning-related synaptic and intrinsic plasticity. Rats received one session of trace fear conditioning, followed by a brief conditioned stimulus (CS) test the next day. To relate behavioral performance with measures of hippocampal CA1 physiology, brain slices were prepared within 1 h of the CS test. In trace-conditioned rats, both synaptic plasticity and intrinsic excitability were significantly correlated with behavior such that better learning corresponded with enhanced long-term potentiation (LTP; r = 0.64, P < 0.05) and a smaller postburst afterhyperpolarization (AHP; r = −0.62, P < 0.05). Such correlations were not observed in pseudoconditioned rats, whose physiological data were comparable to those of poor learners and naive and chamber-exposed control rats. In addition, acquisition of trace fear conditioning did not enhance basal synaptic responses. Thus these data suggest that within the hippocampus both synaptic and intrinsic mechanisms are involved in the acquisition of trace fear conditioning.

scholarly journals Activating mGlu3 metabotropic glutamate receptors rescues schizophrenia-like cognitive deficits through metaplastic adaptations within the hippocampus

2020 ◽  
Author(s):  
Shalini Dogra ◽  
Branden J. Stansley ◽  
Zixiu Xiang ◽  
Weilun Qian ◽  
Rocco G. Gogliotti ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Cognitive Deficits ◽  
Pyramidal Cells ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Metabotropic Glutamate ◽  
Trace Fear Conditioning ◽  
Genetic Deletion ◽  
Trace Fear ◽  
Hippocampal Pyramidal Cells

AbstractBackgroundPolymorphisms in GRM3, the gene encoding the mGlu3 metabotropic glutamate receptor, are associated with impaired cognition and neuropsychiatric disorders such as schizophrenia. Limited availability of selective genetic and molecular tools has hindered progress in developing a clear understanding of the mechanisms through which mGlu3 receptors regulate synaptic plasticity and cognition.MethodsWe examined associative learning in mice with trace fear conditioning, a hippocampal-dependent learning task disrupted in patients with schizophrenia. Underlying cellular mechanisms were assessed using ex vivo hippocampal slice preparations with selective pharmacological tools and selective genetic deletion of mGlu3 receptor expression in specific neuronal subpopulations.ResultsmGlu3 receptor activation enhanced trace fear conditioning and reversed deficits induced by subchronic phencyclidine. Mechanistic studies revealed that mGlu3 receptor activation induced metaplastic changes, biasing afferent stimulation to induce long-term potentiation through a mGlu5 receptor-dependent, endocannabinoid-mediated, disinhibitory mechanism. Selective genetic deletion of either mGlu3 or mGlu5 from hippocampal pyramidal cells eliminated effects of mGlu3 activation, revealing a novel mechanism by which mGlu3 and mGlu5 interact to enhance cognitive function.ConclusionsThese data demonstrate that activation of mGlu3 receptors in hippocampal pyramidal cells enhances hippocampal-dependent cognition in control and impaired mice by inducing a novel form of metaplasticity to regulate circuit function – providing a clear mechanism through which genetic variation in GRM3 can contribute to cognitive deficits. Developing approaches to positively modulate mGlu3 receptor function represents an encouraging new avenue for treating cognitive disruption in schizophrenia and other psychiatric diseases.

Trace Fear Conditioning Detects Hypoxic-Ischemic Brain Injury in Neonatal Mice

2011 ◽  
Vol 33 (3-4) ◽  
pp. 222-230 ◽  
Author(s):  
Katarina Järlestedt ◽  
Alison L. Atkins ◽  
Henrik Hagberg ◽  
Marcela Pekna ◽  
Carina Mallard
Keyword(s):  
Brain Injury ◽  
Fear Conditioning ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Neonatal Mice ◽  
Trace Fear Conditioning ◽  
Hypoxic Ischemic Brain Injury ◽  
Trace Fear

Distance-Dependent Ni2+-Sensitivity of Synaptic Plasticity in Apical Dendrites of Hippocampal CA1 Pyramidal Cells

2002 ◽  
Vol 87 (2) ◽  
pp. 1169-1174 ◽  
Author(s):  
Yoshikazu Isomura ◽  
Yoko Fujiwara-Tsukamoto ◽  
Michiko Imanishi ◽  
Atsushi Nambu ◽  
Masahiko Takada
Keyword(s):  
Calcium Influx ◽  
Critical Role ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Apical Dendrite ◽  
Excitatory Postsynaptic Potential ◽  
Distal Dendrite ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1

Low concentration of Ni2+, a T- and R-type voltage-dependent calcium channel (VDCC) blocker, is known to inhibit the induction of long-term potentiation (LTP) in the hippocampal CA1 pyramidal cells. These VDCCs are distributed more abundantly at the distal area of the apical dendrite than at the proximal dendritic area or soma. Therefore we investigated the relationship between the Ni2+-sensitivity of LTP induction and the synaptic location along the apical dendrite. Field potential recordings revealed that 25 μM Ni2+ hardly influenced LTP at the proximal dendritic area (50 μm distant from the somata). In contrast, the same concentration of Ni2+ inhibited the LTP induction mildly at the middle dendritic area (150 μm) and strongly at the distal dendritic area (250 μm). Ni2+ did not significantly affect either the synaptic transmission at the distal dendrite or the burst-firing ability at the soma. However, synaptically evoked population spikes recorded near the somata were slightly reduced by Ni2+ application, probably owing to occlusion of dendritic excitatory postsynaptic potential (EPSP) amplification. Even when the stimulating intensity was strengthened sufficiently to overcome such a reduction in spike generation during LTP induction, the magnitude of distal LTP was not significantly recovered from the Ni2+-dependent inhibition. These results suggest that Ni2+ may inhibit the induction of distal LTP directly by blocking calcium influx through T- and/or R-type VDCCs. The differentially distributed calcium channels may play a critical role in the induction of LTP at dendritic synapses of the hippocampal pyramidal cells.

Dissociable effects of hippocampus lesions on expression of fear and trace fear conditioning memories in rats

Hippocampus ◽  
2006 ◽  
Vol 16 (2) ◽  
pp. 103-113 ◽  
Author(s):  
Michael A. Burman ◽  
Mark J. Starr ◽  
Jonathan C. Gewirtz
Keyword(s):  
Fear Conditioning ◽  
Trace Fear Conditioning ◽  
Trace Fear

scholarly journals The role of GFAP and vimentin in learning and memory

2019 ◽  
Vol 400 (9) ◽  
pp. 1147-1156 ◽  
Author(s):  
Ulrika Wilhelmsson ◽  
Andrea Pozo-Rodrigalvarez ◽  
Marie Kalm ◽  
Yolanda de Pablo ◽  
Åsa Widestrand ◽  
...  
Keyword(s):  
Object Recognition ◽  
Fear Conditioning ◽  
Morris Water Maze ◽  
Exploratory Behavior ◽  
Water Maze ◽  
Trace Fear Conditioning ◽  
Memory Extinction ◽  
Post Traumatic ◽  
Trace Fear

Abstract Intermediate filaments (also termed nanofilaments) are involved in many cellular functions and play important roles in cellular responses to stress. The upregulation of glial fibrillary acidic protein (GFAP) and vimentin (Vim), intermediate filament proteins of astrocytes, is the hallmark of astrocyte activation and reactive gliosis in response to injury, ischemia or neurodegeneration. Reactive gliosis is essential for the protective role of astrocytes at acute stages of neurotrauma or ischemic stroke. However, GFAP and Vim were also linked to neural plasticity and regenerative responses in healthy and injured brain. Mice deficient for GFAP and vimentin (GFAP−/−Vim−/−) exhibit increased post-traumatic synaptic plasticity and increased basal and post-traumatic hippocampal neurogenesis. Here we assessed the locomotor and exploratory behavior of GFAP−/−Vim−/− mice, their learning, memory and memory extinction, by using the open field, object recognition and Morris water maze tests, trace fear conditioning, and by recording reversal learning in IntelliCages. While the locomotion, exploratory behavior and learning of GFAP−/−Vim−/− mice, as assessed by object recognition, the Morris water maze, and trace fear conditioning tests, were comparable to wildtype mice, GFAP−/−Vim−/− mice showed more pronounced memory extinction when tested in IntelliCages, a finding compatible with the scenario of an increased rate of reorganization of the hippocampal circuitry.

scholarly journals Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

2013 ◽  
Vol 106 ◽  
pp. 316-323 ◽  
Author(s):  
David Cox ◽  
Jennifer Czerniawski ◽  
Fredrick Ree ◽  
Tim Otto
Keyword(s):  
Fear Conditioning ◽  
Time Course ◽  
Trace Fear Conditioning ◽  
Trace Fear
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