Loss of inhibition is suggested to cause pathological pain symptoms. Indeed, some human case reports suggest that lesions including the thalamic reticular nucleus (TRN) which provides major inhibitory inputs to other thalamic nuclei, may induce thalamic pain, a type of neuropathic pain.In support, recent studies demonstrated that activation of GABAergic neurons in the TRN reduces nociceptive responses in mice, reiterating the importance of the TRN in gating nociception. However, whether biochemically distinct neuronal types in the TRN differentially contribute to gating nociception has not been investigated. We, therefore, investigated whether the activity of parvalbumin (PV) and somatostatin (SOM) expressing neurons in the somatosensory TRN differentially modulate nociceptive behaviors using optogenetics and immunostaining techniques. We found that activation of PV neurons in the somatosensory TRN significantly reduced nociceptive behaviors, while activation of SOM neurons in the TRN had no such effect. Also, selective activation of PV neurons, but not SOM neurons, in the TRN activated relatively more PV neurons in the primary somatosensory cortex, which delivers inhibitory effect in the cortex, when measured with cFos and PV double staining. Results of our study suggest that PV neurons in the somatosensory TRN have a stronger influence in regulating nociception and that their activations may provide further inhibition in the somatosensory cortex by activating cortical PV neurons.

The thalamus is a brain structure known to modulate sensory information before relaying to the cortex. The unique ability of a thalamocortical (TC) neuron to switch between the high frequency burst firing and single spike tonic firing has been implicated to have a key role in sensory modulation including pain. Of the two firing modes, burst firing, especially maintaining certain burst firing properties, was suggested to be critical in controlling nociceptive behaviors. Therefore, understanding the factors that influence burst firing properties would offer important insight into understanding sensory modulation. Using computational modeling, we investigated how the balance of excitatory and inhibitory inputs into a TC neuron influence TC bursting properties. We found that intensity of inhibitory inputs and the timing of excitatory input delivery control the dynamics of bursting properties. Then, to reflect a more realistic model, excitatory inputs delivered at different dendritic locations—proximal, intermediate, or distal—of a TC neuron were also investigated. Interestingly, excitatory input delivered into a distal dendrite, despite the furthest distance, had the strongest influence in shaping burst firing properties, suggesting that not all inputs equally contribute to modulating TC bursting properties. Overall, the results provide computational insights in understanding the detailed mechanism of the factors influencing temporal pattern of thalamic bursts.
Brain ; Calcium Channels, T-Type ; Computational Biology ; Dendrites ; Fires ; Neurons ; Sensory Gating ; Thalamus