Abstract
Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.
Highlights
Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation
While it is widely agreed that complete deletion of Nbea in mice leads to defects of spontaneous and evoked synaptic transmission at excitatory and inhibitory s ynapses[4,5,6,7], only some of the defects can be attributed to reduced surface levels of postsynaptic AMPA, NMDA and GABAA receptor subunits[4,7,8,9,10]
long-term potentiation (LTP) at perforant path-to-granule cell (PP-GC) synapses in N bea+/− and wild-type littermate control mice was induced by theta-burst stimulation (TBS) protocols
Summary
Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients. Autism-related abnormalities are present in Nbea+/− mice including altered social behaviours, increased self-grooming, delayed spatial learning and memory, increased conditioned fear responses, and impaired fear memory e xtinction[20,21] Along with these findings, long-term potentiation (LTP) was enhanced in acute slices of the CA1 region of the hippocampus, an important site for spatial learning[20]. We found that N bea+/− mice displayed enhanced LTP of the granule cell population spike, which shows that Nbea has a functional role in vivo that could help explain the behavioural phenotypes observed in haploinsufficient mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
