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Specificity of Primate Amygdalar Pathways to Hippocampus.

The Journal of neuroscience : the official journal of the Society for Neuroscience | 2018

The amygdala projects to hippocampus in pathways through which affective or social stimuli may influence learning and memory. We investigated the still unknown amygdalar termination patterns and their postsynaptic targets in hippocampus from system to synapse in rhesus monkeys of both sexes. The amygdala robustly innervated the stratum lacunosum-moleculare layer of cornu ammonis fields and uncus anteriorly. Sparser terminations in posterior hippocampus innervated the radiatum and pyramidal layers at the prosubicular/CA1 juncture. The terminations, which were larger than other afferents in the surrounding neuropil, position the amygdala to influence hippocampal input anteriorly, and its output posteriorly. Most amygdalar boutons (76-80%) innervated spines of excitatory hippocampal neurons, and most of the remaining innervated presumed inhibitory neurons, identified by morphology and label with parvalbumin or calretinin, which distinguished nonoverlapping neurochemical classes of hippocampal inhibitory neurons. In CA1, amygdalar axons innervated some calretinin neurons, which disinhibit pyramidal neurons. By contrast, in CA3 the amygdala innervated both calretinin and parvalbumin neurons; the latter strongly inhibit nearby excitatory neurons. In CA3, amygdalar pathways also made closely spaced dual synapses on excitatory neurons. The strong excitatory synapses in CA3 may facilitate affective context representations and trigger sharp-wave ripples associated with memory consolidation. When the amygdala is excessively activated during traumatic events, the specialized innervation of excitatory neurons and the powerful parvalbumin inhibitory neurons in CA3 may allow the suppression of activity of nearby neurons that receive weaker nonamygdalar input, leading to biased passage of highly charged affective stimuli and generalized fear.SIGNIFICANCE STATEMENT Strong pathways from the amygdala targeted the anterior hippocampus, and more weakly its posterior sectors, positioned to influence a variety of emotional and cognitive functions. In hippocampal field CA1, the amygdala innervated some calretinin neurons, which disinhibit excitatory neurons. By contrast, in CA3 the amygdala innervated calretinin as well as some of the powerful parvalbumin inhibitory neurons and may help balance the activity of neural ensembles to allow social interactions, learning, and memory. These results suggest that when the amygdala is hyperactive during emotional upheaval, it strongly activates excitatory hippocampal neurons and parvalbumin inhibitory neurons in CA3, which can suppress nearby neurons that receive weaker input from other sources, biasing the passage of stimuli with high emotional import and leading to generalized fear.

Pubmed ID: 30249799 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH057414
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH117785

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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RRID:SCR_002716

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RRID:SCR_001775

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RRID:AB_10000343

This monoclonal targets parvalbumin

View all literature mentions

Calretinin (CR) Antibody (antibody)

RRID:AB_10000320

This monoclonal targets Calretinin (CR)

View all literature mentions

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RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

View all literature mentions

Synapse Web Reconstruct (data processing software)

RRID:SCR_002716

A Windows (Win32) software application for montaging, aligning, tracing, measuring, and reconstructing objects from serial microscopic section images. The software is designed for microscopy in which section resolution is much less than section thickness, such as transmitted electron microscopy (EM) where the resolution is a few nanometers while the section thickness is many tens of nanometers. Reconstruct can easily handle series with hundreds of very large, high-resolution section images. It facilitates image cropping, scaling and alignment. Multiple images can be placed side-by-side to make a montage of a section from a mosaic of images. The alignment of adjacent sections can be rapidly compared by either blending the two sections or by flickering between them. Sections can be moved while blended. Reconstruct aids in the calibration of image size. Images taken at different magnifications can be combined, calibrated and aligned. Tools for tracing and editing of objects on sections are provided. Objects can be surfaced from the traces and previewed in an OpenGL-based 3D scene window. The 3D scene can be saved as a bitmap or as a VRML file.

View all literature mentions

AutoQuant (software resource)

RRID:SCR_002465

Software package of 2D and 3D restoration algorithms.Advanced image deconvolution and 3D visualization software for Life Science Researchers.

View all literature mentions

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RRID:SCR_002526

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View all literature mentions

Neurolucida (software resource)

RRID:SCR_001775

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View all literature mentions

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RRID:AB_2631173

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