A new Northwestern Medicine study identified looped neural connections between the cortex and thalamus, according to findings published in The Journal of Neuroscience.
Runaway excitation of these loops is believed to contribute to epilepsy, making these findings an important first step in understanding the cellular mechanisms of the phenomenon, according to Gordon Shepherd, MD, PhD, associate professor of Physiology and senior author of the study.
“This is a new wiring diagram for how activities flow between the thalamus and the cortex,” Shepherd said. “Now that we’ve identified these cell-type specific connections, we can experimentally test those ideas.”
The thalamus is the sensory hub of the brain, the first stop for sensory information before it makes its way to the cortex; it isn’t a one-way street, however.
For sensory regions of the cortex, the traditional view of this circuit was a division of labor, with corticothalamic (CT) neurons only sending feedback from the cortex to the thalamus, while pyramidal track (PT) neurons in turn only connect to higher-order regions of the thalamus. However, a previous study in the Shepherd laboratory found that in higher-order motor areas, these PT neurons actually connected back to the thalamus to form a closed loop: cortex to thalamus, and then directly back to cortex.
“This appeared to be related to motor planning and short-term memory,” said KuangHua Guo, a sixth-year student in the Medical Scientist Training Program (MSTP) and lead author of the current study.
In this study, Guo, Shepherd and their collaborators examined lower-order sensory regions of the thalamus, involved in processing tactile information from the hands. Measuring activity in single cells using light-sensitive proteins and recording electrical impulses, the investigators found these lower-order regions of the thalamus, through both CT and PT neurons, formed closed loops with higher-order regions of the thalamus.
“This is very different from the classical story of these neurons projecting only forward or backward,” Guo said. “It seems that the lower-order regions of the cortex have similar circuit organization as the higher-order regions.”
In some ways, this is a simplification of what was previously a more complex story, according to Shepherd.
“It shifts the focus back on the direct interaction between one little chunk of the cortex and its little chunk of thalamus,” he said.
Activation of this area of the brain has been implicated in awareness and consciousness, and excessive activation has also been connected to epileptic seizures, though the source of this recurrent over-activation was a mystery, according to Guo.
“Before we knew about these loops, it would be hard to explain how you generate this recurrent activity,” Guo said. “Now we have a suspicion that this PT neuron is mediating that.”
Funding was provided by National Institutes of Health Grants MH067564 and NS061963.