title: Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.
abstract: 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.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Jeanne T
authors.initials: JT
authors.lastname: Paz
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Christian
authors.forename: Isabel
authors.initials: I
authors.lastname: Parada
authors.forename: David A
authors.initials: DA
authors.lastname: Prince
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D017097:Electric Impedance; D005071:Evoked Potentials; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000503:physiopathology; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013787:Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D020747:Calcium Channels, T-Type; D002118:Calcium
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