Neuroscience
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We previously suggested that orientation-tuned surround suppression of responses of cells in the primary visual cortex (V1) is primarily caused by a decrease in geniculocortical input for the cell [Ozeki H, Sadakane O, Akasaki T, Naito T, Shimegi S, Sato H (2004) Relationship between excitation and inhibition underlying size tuning and contextual response modulation in the cat primary visual cortex. J Neurosci 24:1428-1438]. To further test this hypothesis, we compared the strength of orientation and spatial phase selectivity of surround suppression, and the spatial extent of the extraclassical receptive field (ECRF) between the lateral geniculate nucleus (LGN) and V1 neurons of anesthetized cats. ⋯ In 70% of the LGN neurons that exhibited significant orientation-tuned extraclassical surround suppression, the effective orientation of the suppression varied according to a change in the orientation of CRF stimulus, while the remaining 30% exhibited a fixed preferred orientation of the suppression regardless of the orientation of the CRF grating. These results suggest that the basic properties of surround suppression, such as orientation and spatial phase tuning, already exist in cat LGN and that a decrease of surround suppression in excitatory inputs from LGN by surround suppression is the primary cause of surround suppression in V1. Corticogeniculate feedback may further elaborate the properties of surround suppression in LGN.
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Ischemic brain injury is one of the leading causes of epilepsy in the elderly, and there are currently no adult rodent models of global ischemia, unilateral hemispheric ischemia, or focal ischemia that report the occurrence of spontaneous motor seizures following ischemic brain injury. The rodent hypoxic-ischemic (H-I) model of brain injury in adult rats is a model of unilateral hemispheric ischemic injury. Recent studies have shown that an H-I injury in perinatal rats causes hippocampal mossy fiber sprouting and epilepsy. ⋯ Three of 20 lesioned animals (15%) were observed to have at least one spontaneous motor seizure 6-12 months after treatment. Approximately 50% of the ipsilateral and contralateral hippocampal slices displayed abnormal electrophysiological responses in the dentate gyrus, manifest as all-or-none bursts to hilar stimulation. This study suggests that H-I injury is associated with synaptic reorganization in the lesioned region of the hippocampus, and that new recurrent excitatory circuits can predispose the hippocampus to abnormal electrophysiological activity and spontaneous motor seizures.
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Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. ⋯ Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflammatory cytokine mRNA expression (IL-1beta, IL-6, and TNFalpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies.
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Neonatal maternal separation (NMS) has been shown to trigger alterations in neuroendocrine, neurochemical and sensory response to nociceptive stimuli along the brain-gut axis. These alterations may be the result of a cascade of events that are regulated by neurotrophic factors. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for the development and maintenance of sensory neurons and for the formation of central pain circuitry. ⋯ Quantitative analysis of TrkA-ir neurons indicated a significant interactive effect of NMS and CRD on the mean number of TrkA-ir neurons in laminae V-VI of rats, in which significant difference was found between NMS+CRD and NH+CRD. Double immunofluorescence of TrkA and Fos showed that CRD has a significant effect on TrkA expression in Fos-positive neurons in laminae V-VI and lamina X of rats, while no significant difference was found between NMS+CRD and NH+CRD. These results demonstrate that NMS induced alterations in NGF protein level and TrkA expression in adult rat spinal cord and indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia.
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Epileptiform activity induces long term aberrations in hippocampal network functions. This study was conducted in pentylenetetrazol (PTZ) -kindled rats to examine offsetting of aberrations associated with seizure proneness in hippocampus area CA1 by theta pulse stimulation (TPS: 5 Hz trains for 3 min) -induced activity pattern. In hippocampal slices from both control and kindled rats, the field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded through electrodes in the apical dendrites and stratum pyramidale, respectively. ⋯ The lasting depressive effect of TPS on the PS amplitude was converted into facilitation by adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX). Potentiation of the PS amplitude by TPS in the presence of CPX was blocked by an N-methyl-d-aspartate receptor antagonist AP5. We hypothesize that the extracellular adenosine spillover, acting through adenosine A1 receptors, during TPS-induced activity pattern could trigger a homeostatic process for correcting network imbalances caused by epileptiform activity.