
The author explores the impact of Protocadherin10 deficiency in interneurons on socio-affective communication, particularly in relation to Autism Spectrum Disorder.


coremsg

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions associated with deficits in social interaction and communication, together with repetitive behaviors. The cell adhesion molecule Protocadherin10 ( Pcdh10 ) has been implicated in the etiology of ASD. Pcdh10 is expressed in the nervous system during embryonic and early postnatal development and has been linked to neural circuit formation. Here, we show strong expression of Pcdh10 in the ganglionic eminences and in the basolateral complex of the amygdala at mid and late embryonic stages, respectively. Both inhibitory and excitatory neurons expressed Pcdh10 in the basolateral complex at perinatal stages and genes linked to vocalization behavior were enriched in Pcdh10- expressing neurons in adult mice. To further investigate the involvement of Pcdh10 in neurodevelopment with relevance to ASD, and to assess the functional and behavioral consequences of loss of Pcdh10 in basolateral amygdala interneurons, we combined a ubiquitous and a conditional Pcdh10 knockout mouse model. Conditional knockout of Pcdh10 reduced the number of interneurons in the basolateral complex. Both models exhibited altered developmental trajectories of socio-affective communication through isolation-induced ultrasonic vocalizations in neonatal pups, characterized by increased emission rates in heterozygous pups. Furthermore, acoustic call features were affected and heterozygous conditional knockout pups emitted calls characterized by reduced peak frequencies but increased frequency modulation. Additionally, we identified distinct clusters of call subtypes with specific developmental trajectories, suggesting the vocalization repertoire is extensive and dynamic during early life. The nuanced alterations in socio-affective communication at the level of call emission rates, acoustic call features, and clustering of call subtypes were primarily seen in heterozygous pups of the conditional knockout and less prominent in the ubiquitous Pcdh10 knockout, suggesting that changes in anxiety levels associated with Gsh2 -lineage interneurons might drive the observed behavioral effects. Together, this demonstrates that loss of Pcdh10 specifically in interneurons contributes to behavioral alterations in socio-affective communication with relevance to ASD.

### Competing Interest Statement

The authors have declared no competing interest.

*   ASD
    :   Autism Spectrum Disorder
    BLA
    :   Basolateral Amygdala
    BLC
    :   Basolateral complex
    BP
    :   Biological process
    CGE
    :   Caudal ganglionic eminence
    cKO
    :   Conditional knockout
    Ctx
    :   Cortex
    dBFS
    :   Decibels relative to full-scale
    E
    :   Embryonic day
    GABA
    :   Gamma-aminobutyric acid
    GEs
    :   Ganglionic eminences
    GO
    :   Gene ontology
    HCR
    :   Hybridization chain reaction
    He
    :   Heterozygous
    Ho
    :   Homozygous
    HypTh
    :   Hypothalamus
    ISH
    :   In situ hybridization
    KDE
    :   Kernel density estimation
    KO
    :   knockout
    LA
    :   Lateral amygdala
    LGE
    :   Lateral ganglionic eminence
    MGE
    :   Medial ganglionic eminence
    MZ
    :   Mantle zone
    nLOT
    :   Nucleus of the lateral olfactory tract
    NRTC
    :   Non-reverse transcriptase control
    NTC
    :   Non-template control
    P
    :   Postnatal day
    PAG
    :   Periaqueductal grey
    PBS
    :   Phosphate-buffered saline
    Pcdh10
    :   Protocadherin10
    PCR
    :   Polymerase chain reaction
    PFA
    :   Paraformaldehyde
    POA
    :   Preoptic area
    PVDF
    :   Polyvinylidene difluoride
    qPCR
    :   quantitative polymerase chain reaction
    Spt
    :   Septum
    SVZ
    :   Subventricular zone
    Th
    :   Thalamus
    TRN
    :   Thalamic reticular nucleus
    USV
    :   Ultrasonic vocalization
    VMS
    :   Ventropallial migratory stream
    VZ
    :   Ventricular zone
    Wt
    :   Wild-type
    ZI
    :   Zona incerta

Altered Socio-Affective Communication and Amygdala Development in mice with Protocadherin10-deficient Interneurons

impact-of-protocadherin10-on-mouse-amygdala-development-and-communication


Impact of Protocadherin10 on Mouse Amygdala Development and Communication
