Talk abstracts
Talk on Friday 01:05-01:20pm submitted by Danielle Boyle
The differential contributions of excitatory and inhibitory neurons to cortical pathology in a mouse model of autism spectrum disorder
Danielle Boyle (Neuroscience Graduate Program), Devipriyanka Nagarajan (Department of Neuroscience, The Ohio State University), Meretta Hanson (Neuroscience Graduate Program), Jason Wester (Department of Neuroscience, The Ohio State University )
Abstract:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disease considered among the most impactful in the United States. A primary hypothesis of the mechanism underlying ASD is that the ratio of excitation to inhibition (E/I) is imbalanced in the cortex, leading to disrupted information processing. E/I balance depends on the proper development of synaptic connections among subtypes of excitatory projection neurons (PNs) and inhibitory interneuron (INs). Thus, an imbalance in E/I may result from abnormal development of neurons from either population. ARID1B is a high confidence ASD risk gene that is initially expressed during early embryonic development in both excitatory PNs and inhibitory INs. Here, we used transgenic strategies in mice to conditionally knock out (cKO) one copy of Arid1b from either excitatory PNs or a subset of inhibitory INs. We used whole-cell patch clamp recording in acute cortical slices to investigate intrinsic membrane properties and synaptic physiology among mutant and control neurons. Our preliminary data show that cKO of Arid1b from PNs increases their excitability, which may contribute to E/I imbalance. Interestingly, cKO from INs does not alter their intrinsic membrane properties, but does result in non-cell autonomous changes in cortical circuit development. We observe an increase in the amplitude and reliability of excitatory synaptic input from non-mutant PNs onto mutant INs. Although E/I imbalance is typically correlated with pathology, altered synaptic dynamics can act in a compensatory manner in ASD. Previous work reported that Arid1b haploinsufficiency disrupts IN proliferation during embryonic development, resulting in fewer INs in mature neocortex. Our results may reflect a homeostatic mechanism, in which excitatory synaptic strength has increased to compensate for fewer inhibitory cells.
Keywords: cortical development, autism spectrum disorder, excitatory inhibitory balance