scholarly journals Septal GABAergic inputs to CA1 govern contextual memory retrieval

2020 ◽  
Vol 6 (44) ◽  
pp. eaba5003
Author(s):  
Arnau Sans-Dublanc ◽  
Adrià Razzauti ◽  
Srinidhi Desikan ◽  
Marta Pascual ◽  
Hannah Monyer ◽  
...  
Keyword(s):  
Memory Retrieval ◽  
Pyramidal Neurons ◽  
Medial Septum ◽  
Aminobutyric Acid ◽  
Contextual Fear ◽  
Extracellular Signal Regulated Kinase ◽  
Impaired Memory ◽  
Extracellular Signal ◽  
Episodic Memories ◽  
Feed Forward Inhibition

The CA1 output region of the hippocampus plays an essential role in the retrieval of episodic memories. γ-Aminobutyric acid–releasing (GABAergic) long-range projections from the medial septum (MS) densely innervate the hippocampus, but whether septal inputs regulate memory expression remains elusive. We found that the MS to CA1 connection is recruited during recall of a contextual fear memory. Chemogenetic silencing of CA1-projecting MS neurons or septal GABAergic terminals within CA1 blocked memory retrieval. Photostimulation of septal GABAergic terminals in CA1 selectively inhibited interneurons. Abrogating septal GABAergic cells during retrieval disinhibited parvalbumin-rich (PV+) cells in CA1. Direct activation of CA1 PV+ cells impaired memory and prevented the induction of extracellular signal–regulated kinase/mitogen-activated kinase signaling in postsynaptic pyramidal neurons. Opposing disinhibition of hippocampal PV+ cells reversibly restored memory. Our data indicate that suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons is an important mechanism in gating contextual fear behavior.

scholarly journals Septal GABAergic Inputs to CA1 Govern Contextual Memory Retrieval

2019 ◽  
Author(s):  
Arnau Sans-Dublanc ◽  
Adrià Razzauti ◽  
Srinidhi Desikan ◽  
Marta Pascual ◽  
Jaime de la Rocha ◽  
...  
Keyword(s):  
Memory Retrieval ◽  
Pyramidal Cells ◽  
Fear Memory ◽  
Medial Septum ◽  
Gabaergic Neurons ◽  
Contextual Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Feed Forward Inhibition ◽  
Fear Behavior

AbstractWhether projections from the medial septum regulate the function of the CA1 hippocampus in episodic memory retrieval is not known. Here we show that septal GABAergic inputs to CA1 promote contextual fear memory, blocking the activation of parvalbumin-rich interneurons to facilitate Erk/MAP-kinase signaling in pyramidal cells during retrieval. Thus, suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons gates contextual fear behavior.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury–induced Mechanical Hypersensitivity and Glial Extracellular Signal–regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus

2016 ◽  
Vol 125 (6) ◽  
pp. 1202-1218 ◽  
Author(s):  
Chun-Ta Huang ◽  
Seu-Hwa Chen ◽  
June-Horng Lue ◽  
Chi-Fen Chang ◽  
Wen-Hsin Wen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Median Nerve ◽  
Nerve Injury ◽  
Type A ◽  
Aminobutyric Acid ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Acid Type ◽  
Extracellular Signal ◽  
Median Nerve Injury

Abstract Background Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. Methods We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. Results At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. Conclusions Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

scholarly journals Imaging and optogenetically manipulating recent and very remote memories reveals that CA1 is required for retrieving gist memories over time and CA3 for memory precision

2020 ◽  
Author(s):  
Erika Atucha ◽  
Shih-pi Ku ◽  
Michael Friis Lippert ◽  
Frank Walter Ohl ◽  
Magdalena Sauvage
Keyword(s):  
Memory Retrieval ◽  
Contextual Fear Conditioning ◽  
Remote Memory ◽  
Memory Representation ◽  
Contextual Fear ◽  
Cortical Areas ◽  
Causal Approach ◽  
Episodic Memories ◽  
Memory Precision ◽  
Over Time

Episodic memories are hippocampus dependent. Over time such memories undergo consolidation and are thought to transition from precise to gist memories and additionally engage neocortical areas. Whether remote memories still depend on the hippocampus remains a controversy that might stem from the difficulties to distinguish activity from CA1 and CA3 subregions in the hippocampus. CA3 is thought to perform computations that are more time sensitive than CA1 such as pattern completion (completion of a full memory representation based on details). Since details fade over time, we predicted that CA3 would no longer contribute to memory retrieval for very remote memory traces. Further, the contribution of parahippocampal cortical areas which tightly interact with the hippocampus is not well understood. We recently published that indeed CA3 plays a time-limited role in the retrieval of memory while CA1 remains engaged for up to 1-year (equivalent to 40-years-old memory in humans) and that parahippocampal cortical areas were increasingly engaged over time. Here we study the contribution of CA1 and CA3 to the nature (gist/precise) of memory retrieval for recent and up to 1-year-old remote memories using a causal approach. We combined optogenetic cell firing inhibition in CA1 and CA3 with a contextual fear conditioning task to investigate memory precision and measured the neuroanatomical correlates using Arc imaging. While CA3 is required for memory precision at recent time points CA1 contributed to retrieving gist memories independently of the age of the memory trace with the support of the parahippocampal areas for the most remote memories.

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