Research Highlight July 11, 2016

Is there interconnectivity between neurons in the thalamic reticular nucleus?

Is there interconnectivity between neurons in the thalamic reticular nucleus?

The thalamus is a region of the brain involved with sensory detection and regulation of consciousness, sleep and alertness. An associated structure, the thalamic reticular nucleus (TRN), is a sheet of GABAergic neurons set in the path of axons connecting the thalamus and cortex. The TRN regulates transfer of information from the thalamus to the cortex by providing the major inhibitory input to the thalamic neurons that project to the cortex. Its dysfunction has been associated with epilepsy and schizophrenia.

A long-standing question in the study of thalamic function is whether TRN neurons form GABAergic synapses with other TRN neurons. It has been proposed that intra-TRN GABAergic connections serve important functions in normal and disease states. However, the existence of such connections has been a controversial topic. In a paper published July 6 in The Journal of Neuroscience, JAX Associate Professor Zhong-Wei Zhang presents data obtained using optogenetic and genetic methods to investigate the existence of intra-TRN GABAergic synapses in mice. Interestingly, he finds them, but not for long.

Zhang and colleagues first expressed channelrhodopsin throughout the TRN so that light could be used to stimulate TRN neurons and their axons, allowing for analysis of the synaptic responses. What they observed through optogenetics was that there was light-evoked GABAergic synaptic activity in mice younger than two weeks of age, but that it disappeared thereafter. Next, they genetically blocked GABAergic transmission from TRN neurons. They observed that this manipulation does not change GABAergic synaptic activity recorded from TRN neurons, indicating that GABAergic inputs come from external rather than intra-TRN sources.

All told, the data show that except for a brief period immediately after birth, the vast majority and perhaps all of GABAergic inputs to the TRN come from elsewhere in the brain. These findings help clarify a long-standing debate. Further studies are needed to investigate these connections and their physiological roles.

Hou G, Smith AG, Zhang Z-W. 2016. Lack of Intrinsic GABAergic Connections in the Thalamic Reticular Nucleus of the Mouse. The Journal of Neuroscience 36(27):7246-7252.

DOI:10.1523/JNEUROSCI.0607-16.2016