Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome

Presented here are a series of four single-cell electrophysiology experiments detailing the function of inhibitory and excitatory processes in the anterior piriform cortex. The normal function and neurophysiology of this area is contrasted with that of a mouse model of the genetic disorder Fragile X Syndrome, a pleiotropic disorder that is hypothesized to be characterized by improper excitatory/inhibitory balance in a number of brain regions. Analysis of quantal inhibitory neurotransmission provided the most comprehensive report of synaptic inhibition in the piriform cortex to date. This study revealed no deficit in the synaptic properties of Fragile X Syndrome mice. Event amplitude, shape statistics, and interevent timing parameters were all in close agreement between the two groups. Tonic inhibitory conductance was found to be comparable between genotypes as well, in contrast to several published reports of compromised tonic inhibition in this disease model. A measure of the cellular response to evoked stimulation was performed, testing the function of a known fast inhibitory microcircuit. This experiment showed that both Fragile X Syndrome and control animals exhibit tight inhibitory control of evoked excitation at moderate and high stimulation levels. Additionally, a paired pulse test demonstrated that, while excitatory currents increase in response to quickly arriving stimuli, feedforward inhibition scales as well, maintaining the inhibitory/excitatory balance. The cellular response to bursting stimulation was assessed for each genotype at a holding potential of -70mV and at the native resting membrane potential for each cell, both in the absence and presence of pharmacological blockade of NMDA-type glutamatergic receptors. A significant deficit in NMDA receptor-mediated current was observed in the burst response of Fragile X Syndrome cells but not in controls. It was also shown in control animals that NMDA receptors participate in the excitatory response to a single burst of stimuli, an unexpected finding that suggests unique integrative processes in the anterior piriform cortex with respect to homologous brain structures.