Cortico-Thalamic Circuit Interactions in Normal Development and ASD
Sensory processing is a feature that is disrupted in children with ASD. All sensory information, with the exception of olfaction, is transmitted from the external environment to the thalamus, where it is processed and integrated before it is relayed to the cortex. During development, there is a period of great plasticity that occurs in both the thalamus and cortex. Interestingly, the critical periods in these two structures overlap in time. Our hypothesis is that in a number of genetic and non-genetic mouse models of Autism Spectrum Disorders defects in either cortex or thalamus leads to a progressive disruption of development in the connections between the two structures. To test this hypothesis, the Chen and Fagiolini Labs are using the visual system as an experimental model, because it is the best understood mammalian sensory system. A combination of in vitro and in vivo electrophysiology and behavioral testing are used to study the development and plasticity of thalamic and cortical microcircuits in a number of genetic and non-genetic mouse models for ASD.
To determine the importance of cortical-thalamic interaction during development of the visual pathway, we are also performing experiments to selectively perturb cortical function while analyzing retinogeniculate development. We have performed pilot experiments where we inject muscimol, a GABAergic agonist, into V1 of the visual cortex between the ages of P20-P27. Intrinsic cortical imaging of these animals after this procedure demonstrates effective reduction of visual-evoked activity in the cortex. Our preliminary data shows a significant difference in retinogeniculate synaptic strength and innervation in mice whose visual cortex is injected with muscimol when compared to those injected with saline. The average single fiber strength is significantly reduced, and the average number of inputs that innervate a relay neuron is significantly increased in muscimol-injected animals. These results are consistent with our hypothesis that cortical feedback can influence the development of a feedforward circuit. We are currently verifying these results with controls and with experiments that manipulate cortical function in different ways.