Focal Cortical Infarcts Alter Intrinsic Excitability and Synaptic Excitation in the Reticular Thalamic Nucleus

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 04/2010; 30(15):5465-79. DOI: 10.1523/JNEUROSCI.5083-09.2010
Source: PubMed


Focal cortical injuries result in death of cortical neurons and their efferents and ultimately in death or damage of thalamocortical relay (TCR) neurons that project to the affected cortical area. Neurons of the inhibitory reticular thalamic nucleus (nRT) receive excitatory inputs from corticothalamic and thalamocortical axons and are thus denervated by such injuries, yet nRT cells generally survive these insults to a greater degree than TCR cells. nRT cells inhibit TCR cells, regulate thalamocortical transmission, and generate cerebral rhythms including those involved in thalamocortical epilepsies. The survival and reorganization of nRT after cortical injury would determine recovery of thalamocortical circuits after injury. However, the physiological properties and connectivity of the survivors remain unknown. To study possible alterations in nRT neurons, we used the rat photothrombosis model of cortical stroke. Using in vitro patch-clamp recordings at various times after the photothrombotic injury, we show that localized strokes in the somatosensory cortex induce long-term reductions in intrinsic excitability and evoked synaptic excitation of nRT cells by the end of the first week after the injury. We find that nRT neurons in injured rats show (1) decreased membrane input resistance, (2) reduced low-threshold calcium burst responses, and (3) weaker evoked excitatory synaptic responses. Such alterations in nRT cellular excitability could lead to loss of nRT-mediated inhibition in relay nuclei, increased output of surviving TCR cells, and enhanced thalamocortical excitation, which may facilitate recovery of thalamic and cortical sensory circuits. In addition, such changes could be maladaptive, leading to injury-induced epilepsy.

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    • "VPM neurons receive innervations from the thalamic reticular nucleus (TRN), which consists of GABAergic circuits that cover most of the rostral, lateral and ventral parts of the thalamus (Figure 8) [19]. The TRN inhibitory GABAergic cells and their interconnected networks are particularly well suited for the generation of spindle oscillations (7–14 Hz) that characteristically appear during early stages of sleep and anesthesia [20]. "
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    • "The spike morphology and polarity of these latter discharges consistently matched those of typical SWDs and could occur between or after SWDs, suggesting the discharges might represent non-propagating absence events and raised the possibility that cortical lesions could injure or ablate focal cortical generators of SWDs and disrupt their network propagation. Importantly, cortical photothrombosis has been used recently to study the survival and reorganization of neurons of the inhibitory reticular thalamic nucleus, which regulate thalamocortical transmission and generate cerebral rhythms, including those involved in thalamocortical epilepsies (Paz et al., 2010). "
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