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Autism spectrum disorders (ASDs) arise from altered development of the central nervous system, and manifest behaviorally as social interaction deficits and restricted and repetitive behaviors. Alterations to parvalbumin (PV) expressing interneurons have been implicated in the neuropathological and behavioral deficits in autism. In addition, perineuronal nets (PNNs), specialized extracellular matrix structures that enwrap the PV-expressing neurons, also may be altered, which compromises neuronal function and susceptibility to oxidative stress. In particular, the prefrontal cortex (PFC), which regulates several core autistic traits, relies on the normal organization of PNNs and PV-expressing cells, as well as other neural circuit elements. Consequently, we investigated whether PNNs and PV-expressing cells were altered in the PFC of the CNTNAP2 knockout mouse model of ASD and whether these contributed to core autistic-like behaviors in this model system. We observed an overexpression of PNNs, PV-expressing cells, and PNNs enwrapping PV-expressing cells in adult CNTNAP2 mice. Transient digestion of PNNs from the prefrontal cortex (PFC) by injection of chondroitinase ABC in CNTNAP2 mutant mice rescued some of the social interaction deficits, but not the restricted and repetitive behaviors. These findings suggest that the neurobiological regulation of PNNs and PVs in the PFC contribute to social interaction behaviors in neurological disorders including autism.
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This content will become publicly available on December 10, 2025
In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis
Abstract Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap). Instead, genes that encode proteins upstream from the SK current are correlated with dAdap, a finding validated by a different dataset from the mouse’s primary motor cortex that includes pyramidal cells and interneurons, as well as physiological datasets from multiple regions of macaque monkeys. Finally, we construct a minimal model to reproduce observed heterogeneity across cells, with testable predictions.
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- Award ID(s):
- 2015276
- PAR ID:
- 10616358
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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