Hippocampal Interneurons Shape Spatial Coding Alterations in Neurological Disorders

Hippocampal interneurons (INs) play a fundamental role in regulating neural oscillations, modulating excitatory circuits, and shaping spatial representation. While historically overshadowed by excitatory pyramidal cells in spatial coding research, recent advances have demonstrated that inhibitory IN...

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Bibliographic Details
Published in:	Molecular neurobiology Vol. 62; no. 11; pp. 14777 - 14800
Main Authors:	Ikebara, Juliane Midori, Jorge, Renata Silva, Marinho, Luciana Simões Rafagnin, Higa, Guilherme Shigueto Vilar, Adhikari, Avishek, Reis, Fernando M. C. V., Borges, Fernando S., Ulrich, Henning, Takada, Silvia Honda, De Pasquale, Roberto, Kihara, Alexandre Hiroaki
Format:	Journal Article
Language:	English
Published:	New York Springer US 01.11.2025 Springer Nature B.V
Subjects:	Alzheimer's disease Animals Biomedical and Life Sciences Biomedicine Brain research Calcium imaging Calretinin Cell Biology Cholecystokinin Cognition & reasoning Cognitive ability Epilepsy Genetics Hippocampus Hippocampus - pathology Hippocampus - physiopathology Humans Hypoxia Information processing Interneurons Interneurons - metabolism Interneurons - pathology Ischemia Memory Nervous System Diseases - pathology Nervous System Diseases - physiopathology Neural coding Neurobiology Neurodegenerative diseases Neuroimaging Neurological diseases Neurological disorders Neurology Neurons Neurosciences Optics Parvalbumin Peptides Pyramidal cells Review Rhythm Somatostatin Spatial memory Therapeutic applications Traumatic brain injury Temporal lobe epilepsy Hippocampal interneurons Spatial coding Inhibitory circuit dysfunction Alzheimer's disease Theta-gamma coupling
ISSN:	0893-7648, 1559-1182, 1559-1182
Online Access:	Get full text
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Summary:	Hippocampal interneurons (INs) play a fundamental role in regulating neural oscillations, modulating excitatory circuits, and shaping spatial representation. While historically overshadowed by excitatory pyramidal cells in spatial coding research, recent advances have demonstrated that inhibitory INs not only coordinate network dynamics but also contribute directly to spatial information processing. This review aims to provide a novel integrative perspective on how distinct IN subtypes participate in spatial coding and how their dysfunction contributes to cognitive deficits in neurological disorders such as epilepsy, Alzheimer’s disease (AD), traumatic brain injury (TBI), and cerebral hypoxia–ischemia. We synthesize recent findings demonstrating that different IN classes—including parvalbumin (PV)-, somatostatin (SST)-, cholecystokinin (CCK)-, and calretinin (CR)-expressing neurons—exhibit spatially selective activity, challenging traditional views of spatial representation, and influence memory consolidation through network-level interactions. By leveraging cutting-edge techniques such as in vivo calcium imaging and optogenetics, new evidence suggests that INs encode spatial information with a level of specificity previously attributed only to pyramidal cells. Furthermore, we investigate the impact of inhibitory circuit dysfunction in neurological disorders, examining how disruptions in interneuronal activity lead to impaired theta-gamma coupling, altered sharp wave ripples, and destabilized place cell representations, ultimately resulting in spatial memory deficits. This review advances the field by shifting the focus from pyramidal-centered models to a more nuanced understanding of the hippocampal network, emphasizing the active role of INs in spatial coding. By highlighting the translational potential of targeting inhibitory circuits for therapeutic interventions, we propose novel strategies for restoring hippocampal network function in neurological conditions. Readers will gain a comprehensive understanding of the emerging role of INs in spatial representation and the critical implications of their dysfunction, paving the way for future research on interneuron-targeted treatments for cognitive disorders.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	0893-7648 1559-1182 1559-1182
DOI:	10.1007/s12035-025-05020-2