Article

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: 6.75). 04/2010; 30(15):5465-79. DOI: 10.1523/JNEUROSCI.5083-09.2010
Source: PubMed

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.

0 Followers
 · 
111 Views
 · 
6 Downloads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Interaction with the gamma-aminobutyric-acid-type-A (GABAA) receptors is recognized as an important component of the mechanism of propofol, a sedative-hypnotic drug commonly used as anesthetic. However the contribution of GABAA receptors to the central nervous system suppression is still not well understood, especially in the thalamocortical network. In the present study, we investigated if intracerebral injection of bicuculline (a GABAA receptor antagonist) into the thalamus ventral posteromedial nucleus (VPM, a thalamus specific relay nuclei that innervated S1 mostly) could reverse propofol-induced cortical suppression, through recording the changes of both spontaneous and somatosensory neural activities in rat's somatosensory cortex (S1). We found that after injection of bicuculline into VPM, significant increase of neural activities were observed in all bands of local field potentials (total band, 182±6%), while the amplitude of all components in somatosensory evoked potentials were also increased (negative, 121±9% and positive, 124±6%).These data support that the potentiation of GABAA receptor-mediated synaptic inhibition in a thalamic specific relay system seems to play a crucial role in propofol-induced cortical suppression in the somatosensory cortex of rats.
    PLoS ONE 12/2013; 8(12):e82377. DOI:10.1371/journal.pone.0082377 · 3.23 Impact Factor
    • "The T-type calcium channels are present ubiquitously in the brain including the cortex (Perez-Reyes, 2003), and their chronic inhibition in regular cannabis users during brain development might alter cortical network activity in the long-term, and perhaps lead to up or down regulation of these channels in young cannabis users. In keeping with this, it has been shown that a marked adaptive plasticity occurs in the TRN in response to cortical injury leading to augmented excitatory input in uninjured corticothalamic fibers (Paz et al., 2010). Moreover, sleep spindles, resulting from an interplay of actions of these channels, are known to contribute to brain plasticity both in adulthood and during development, and hence, any profound chronic effect on their genesis should be matter of concern (Fogel and Smith, 2011; Khazipov and Luhmann, 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of cannabis in the etiology of schizophrenia has been documented as possibly the strongest environmental risk factor. However, the pathomechanism whereby cannabis use increases this risk has not yet been identified. We argue that this pathomechanism may involve direct effects of exogenous cannabinoids on T-type calcium channels in the thalamus. These channels are crucial for amplification of corticothalamic inputs, as well as for the ability of the thalamus to generate neuronal burst firing. Cortically induced thalamic burst firing has been found to be important in trans-thalamic cortico-cortical interactions. Therefore, any potential interference with the burst firing mode in the thalamus could lead to an impairment in these interactions, which in turn causes a relative disconnection between cortical areas. This in turn could result in reduced ability to recognize re-afferent sensory inputs and psychosis. We also argue that the effects of Δ9THC are more detrimental compared with the effects of cannabidiol, as the former may increase the excitability of thalamic neurons by its direct effect on T-type calcium channels.
    Neuroscience & Biobehavioral Reviews 05/2013; 37(4):658–667. DOI:10.1016/j.neubiorev.2013.02.013 · 10.28 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rodent models of absence seizures are used to investigate the network properties and regulatory mechanisms of the seizure's generalized spike and wave discharge (SWD). As rats age, SWDs occur more frequently, suggesting aging-related changes in the regulation of the corticothalamic mechanisms generating the SWD. We hypothesized that brain resetting mechanisms - how the brain "resets" itself to a more normal functional state following a transient period of abnormal function, e.g., a SWD - are impaired in aged animals and that brain infarction would further affect these resetting mechanisms. The main objective of this study was to determine the effects of aging, infarction, and their potential interaction on the resetting of EEG dynamics assessed by quantitative EEG (qEEG) measures of linear (signal energy measured by amplitude variation; signal frequency measured by mean zero-crossings) and nonlinear (signal complexity measured by the pattern match regularity statistic and the short-term maximum Lyapunov exponent) brain EEG dynamics in 4- and 20-month-old F344 rats with and without brain infarction. The main findings of the study were: 1) dynamic resetting of both linear and nonlinear EEG characteristics occurred following SWDs; 2) animal age significantly affected the degree of dynamic resetting in all four qEEG measures: SWDs in older rats exhibited a lower degree of dynamic resetting; 3) infarction significantly affected the degree of dynamic resetting only in terms of EEG signal complexity: SWDs in infarcted rats exhibited a lower degree of dynamic resetting; and 4) in all four qEEG measures, there was no significant interaction effect between age and infarction on dynamic resetting. We conclude that recovery of the brain to its interictal state following SWDs was better in young adult animals compared with aged animals, and to a lesser degree, in age-matched controls compared with infarction-injured animal groups, suggesting possible effects of brain resetting mechanisms and/or the disruption of the epileptogenic network that triggers SWDs.
    Experimental Neurology 07/2011; 232(1):15-21. DOI:10.1016/j.expneurol.2011.07.004 · 4.62 Impact Factor
Show more

Preview

Download
6 Downloads
Available from