Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr;225(3):1019-1032.
doi: 10.1007/s00429-020-02055-0. Epub 2020 Mar 18.

Decreased density of cholinergic interneurons in striatal territories in Williams syndrome

Kari L Hanson  1   2 , Caroline H Lew  1 , Branka Hrvoj-Mihic  1 , Deion Cuevas  1 , Demi M Z Greiner  1 , Kimberly M Groeniger  1 , Melissa K Edler  3 , Eric Halgren  4   5   6 , Ursula Bellugi  7 , Mary Ann Raghanti  3 , Katerina Semendeferi  8   9
Affiliations

Decreased density of cholinergic interneurons in striatal territories in Williams syndrome

Kari L Hanson et al. Brain Struct Funct. 2020 Apr.

Abstract

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by the hemideletion of approximately 25-28 genes at 7q11.23. Its unusual social and cognitive phenotype is most strikingly characterized by the disinhibition of social behavior, in addition to reduced global IQ, with a relative sparing of language ability. Hypersociality and increased social approach behavior in WS may represent a unique inability to inhibit responses to specific social stimuli, which is likely associated with abnormalities of frontostriatal circuitry. The striatum is characterized by a diversity of interneuron subtypes, including inhibitory parvalbumin-positive interneurons (PV+) and excitatory cholinergic interneurons (Ch+). Animal model research has identified an important role for these specialized cells in regulating social approach behavior. Previous research in humans identified a depletion of interneuron subtypes associated with neuropsychiatric disorders. Here, we examined the density of PV+ and Ch+ interneurons in the striatum of 13 WS and neurotypical (NT) subjects. We found a significant reduction in the density of Ch+ interneurons in the medial caudate nucleus and nucleus accumbens, important regions receiving cortical afferents from the orbitofrontal and ventromedial prefrontal cortex, and circuitry involved in language and reward systems. No significant difference in the distribution of PV+ interneurons was found. The pattern of decreased Ch+ interneuron densities in WS differs from patterns of interneuron depletion found in other disorders.

Keywords: Basal ganglia; Interneurons; Striatum; Williams syndrome.

PubMed Disclaimer

Conflict of interest statement

Compliance with ethical standards

Conflict of interest The authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Examples of neurons and fibers positively stained for ChAT+ in NT (left) and WS (right) subjects in five striatal regions of interest including the dorsal (a, b) and medial (c, d) caudate, dorsal (e, f) and medial (g, h) putamen, and nucleus accumbens (i, j) regions. Arrows denote incomplete cell bodies of neurons that did not meet inclusion criteria. Scale bar = 50 um
Fig. 2
Fig. 2
Examples of neurons and fibers positively stained for PV in NT (left) and WS (right) subjects in four striatal regions of interest including the dorsal (a, b) and medial (c, d) caudate, dorsal (e, f) and medial (g, h) putamen regions. Arrows denote incomplete cell bodies of neurons that did not meet inclusion criteria. Scale bar = 50 um
Fig. 3
Fig. 3
Regions of interest sampled corresponding to the dorsal (dC) and medial (mC) caudate nucleus, medial putamen (mP), dorsal putamen (dP), and nucleus accumbens (NA) regions. Dorsal regions of the putamen and dorsomedial regions of the caudate receive overlapping sensorimotor and associative projections. Adapted from Bernácer et al. (2007); Haber and Knutson (2010); Averbeck et al. (2014)
Fig. 4
Fig. 4
Results of stereological analyses for Ch+ interneuron density. A significantly lower density of Ch+ interneurons was found in the medial caudate (mC) and nucleus accumbens (NAcc) regions, but not in the putamen
Fig. 5
Fig. 5
Results of stereological analyses for PV+ interneuron density. No significant difference in the density of PV+ interneurons was observed between WS and NT subjects
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Adorjan I, Ahmed B, Feher V et al. (2017) Calretinin interneuron density in the caudate nucleus is lower in autism spectrum disorder. Brain 140(7):2028–2040. 10.1093/brain/awx131 - DOI - PMC - PubMed
    1. Atkinson J, Braddick O, Anker S et al. (2003) Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function. Dev Neuropsychol 23:139–172. 10.1080/87565641.2003.9651890 - DOI - PubMed
    1. Atkinson J, Anker S, Braddick O et al. (2007) Visual and visuospatial development in young children with Williams syndrome. Dev Med Child Neurol 43:330–337. 10.1111/j.1469-8749.2001.tb00213.x - DOI - PubMed
    1. Balsters JH, Mantini D, Wenderoth N (2017) Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder. Neuroimage. 10.1016/j.neuroimage.2017.02.019 - DOI - PubMed
    1. Barger N, Hanson KL, Teffer K et al. (2014) Evidence for evolutionary specialization in human limbic structures. Front Hum Neurosci 8:277. 10.3389/fnhum.2014.00277 - DOI - PMC - PubMed