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Disturbances in olfactory processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the olfactory system in ASD remains unclear. Therefore, the present study aimed to evaluate selected components of the GABAergic system in olfactory brain regions and primary olfactory neurons isolated from <jats:italic>Shank3<\/jats:italic>-deficient (<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, which are known for their autism-like behavioral phenotype. <jats:italic>Shank3<\/jats:italic> deficiency led to a significant reduction in GEPHYRIN\/GABA<jats:sub>A<\/jats:sub>R colocalization in the piriform cortex and in primary neurons isolated from the olfactory bulb, while no change of cell morphology was observed. Gene expression analysis revealed a significant reduction in the mRNA levels of <jats:italic>GABA transporter 1<\/jats:italic> in the olfactory bulb and <jats:italic>Collybistin<\/jats:italic> in the frontal cortex of the <jats:italic>Shank3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice compared to WT mice. A similar trend of reduction was observed in the expression of <jats:italic>Somatostatin<\/jats:italic> in the frontal cortex of <jats:italic>Shank3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. The analysis of the expression of other GABAergic neurotransmission markers did not yield statistically significant results. Overall, it appears that <jats:italic>Shank3<\/jats:italic> deficiency leads to changes in GABAergic synapses in the brain regions that are important for olfactory information processing, which may represent basis for understanding functional impairments in autism.<\/jats:p>","DOI":"10.1007\/s11064-023-04097-2","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T07:01:33Z","timestamp":1704524493000},"page":"1008-1016","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas"],"prefix":"10.1007","volume":"49","author":[{"given":"Denisa","family":"Mihalj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Borbelyova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdeno","family":"Pirnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Bacova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ostatnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"issue":"6","key":"4097_CR1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3390\/brainsci10060362","volume":"10","author":"JR Sweigert","year":"2020","unstructured":"Sweigert JR, St John T, Begay KK, Davis GE, Munson J, Shankland E, Estes A, Dager SR, Kleinhans NM (2020) Characterizing olfactory function in children with Autism Spectrum disorder and children with sensory Processing Dysfunction. 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