Loss of function variants in the tuberous sclerosis complex (TSC) result in alterations in both excitatory and inhibitory neurotransmission; however, it is not known whether the dysregulated neurotransmission and subsequent dysfunctional synaptic activity is driven by a specific neuronal population during development. I am interested in the effects of Tsc2 deficiency on interneuron-mediated neurotransmission across early development, as well as whether interneuron-specific loss of Tsc2 drives the synaptic changes in network activity through mTOR-mediated changes in protein expression. By delineating the developmental basis and specific contribution that changes in interneuron-mediated neurotransmission have on synaptic activity, my proposed research will advance our understanding of the basic mechanisms underlying decreased inhibitory signaling observed in TSC-associated epilepsy and identify new potential therapeutic targets. Using RNA-seq to determine the molecular identification of the TSC-interneuron transcriptome and TRAP with ribosome profiling to determine the TSC-interneuron translatome, these experiments will determine the identity and functional consequences of the TSC cortical interneuron translatome and offer critical insight into the basic mechanisms mediating decreased inhibitory signaling in TSC-associated epilepsy.​

Catherine Salussolia, MD, PhD