Journal Article

DZNE-2026-00602

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Depletion of Neurocan in the Prefrontal Cortex Impairs Temporal Order Recognition, Cognitive Flexibility and Perisomatic GABAergic Innervation.

Baidoe-Ansah, D. (First author)DZNE* ; Carceller, H. ; Mirzapourdelavar, H.DZNE* ; Pérez-Rando, M. ; Strackeljan, L.DZNE* ; Garcia-Vazquez, B. ; Seidenbecher, C. ; Kaushik, R.DZNE* ; Nacher, J. ; Dityatev, A. (Last author)DZNE*

2026
Springer Science + Business Media B.V Dordrecht

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Please use a persistent id in citations: doi:10.1007/s10571-026-01762-2

Abstract: The condensed form of the neural extracellular matrix (ECM), known as perineuronal nets (PNNs), is predominantly associated with parvalbumin-expressing (PV+) interneurons in the cortex and hippocampus. PNNs are enriched in lecticans, including neurocan (Ncan). Genetic variation in the human Ncan gene has been linked to alterations in hippocampus-dependent memory, structural differences in the prefrontal cortex (PFC), and increased risk for schizophrenia and bipolar disorder. However, the specific contribution of Ncan to PFC-dependent cognitive functions and synaptic organization remains incompletely understood. Here, we investigated the consequences of region-specific reduction of Ncan in the infralimbic cortex of mice, a region considered homologous to the dorsomedial part of the human medial PFC. Using intracortical adeno-associated virus delivery of shRNA targeting Ncan, we examined PNN-associated markers, synaptic organization, and PFC-dependent behaviors. Ncan knockdown was associated with reduced Wisteria floribunda agglutinin (WFA) labeling of PNNs surrounding PV+ interneurons, suggesting alterations in PNN composition. Behaviorally, mice with reduced Ncan expression exhibited mild but consistent impairments in medial PFC-dependent temporal order recognition memory and in aspects of reversal spatial learning in a labyrinth task. At the cellular level, immunohistochemical analyses revealed a reduction in markers associated with perisomatic GABAergic innervation of PV+ interneurons, together with an increase in the density of vGLUT1-immunopositive puncta in the surrounding neuropil. These structural changes were not observed in constitutive Ncan knockout mice, suggesting the presence of compensatory mechanisms in this model. Together, our findings highlight a functional role of Ncan in supporting perisomatic GABAergic innervation, temporal order recognition memory and cognitive flexibility, important cognitive resources impaired in neuropsychiatric disorders.

Keyword(s): Cognitive flexibility ; Extracellular matrix ; GABAergic synapse ; Glutamatergic synapse ; Neurocan ; Perineuronal net ; Perisomatic inhibition ; Temporal order recognition memory

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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