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1.  Physiological Slowing and Upregulation of Inhibition in Cortex Are Correlated with Behavioral Deficits in Protein Malnourished Rats 
PLoS ONE  2013;8(10):e76556.
Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD) diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the ‘Gap-crossing’ (GC) task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4) neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3) neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls) and much smaller increase in NMDAR1 (12-20%), suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.
doi:10.1371/journal.pone.0076556
PMCID: PMC3789706  PMID: 24098531
2.  NaV1.8 channels are expressed in large, as well as small, diameter sensory afferent neurons 
Channels  2013;7(1):34-37.
Sensory neurons in the dorsal root ganglia (DRG) express a subset of voltage dependent sodium channels (NaV) including NaV1.1, 1.6, 1.7, 1.8 and 1.9. Previous work supported preferential localization of NaV1.8 channels to small-medium diameter, nociceptive afferent neurons. However, we recently published evidence that NaV1.8 was the dominant NaV channel expressed in the somas of small, medium and large diameter muscle afferent neurons, which is consistent with other reports. Here, we extend those results to show that NaV1.8 expression is not correlated with afferent neuron diameter. Using immunocytochemistry, we found NaV1.8 expression in ~50% of sensory afferent neurons with diameters ranging from 20 to 70 µm. In addition, electrophysiological analysis shows that the kinetic and inactivation properties of NaV1.8 current are invariant with neuron size. These data add further support to the idea that NaV1.8 contributes to the electrical excitability of both nociceptive and non-nociceptive sensory neurons.
doi:10.4161/chan.22445
PMCID: PMC3589279  PMID: 23064159
cutaneous afferents; muscle afferents; dorsal root ganglia neurons; Tetrodotoxin-resistant (TTX-R)
3.  The effect of striatal dopaminergic grafts on the neuronal activity in the substantia nigra pars reticulata and subthalamic nucleus in hemiparkinsonian rats 
Brain  2011;134(11):3276-3289.
The electrophysiological correlates of parkinsonism in the basal ganglia have been well studied in patients with Parkinson's disease and animal models. Separately, striatal dopaminergic cell transplantation has shown promise in ameliorating parkinsonian motor symptoms. However, the effect of dopaminergic grafts on basal ganglia electrophysiology has not thoroughly been investigated. In this study, we transplanted murine foetal ventral mesencephalic cells into rats rendered hemiparkinsonian by 6-hydroxydopamine injection. Three months after transplantation, extracellular and local field potential recordings were taken under urethane anaesthesia from the substantia nigra pars reticulata and subthalamic nucleus along with cortical electroencephalograms and were compared to recordings from normal and hemiparkinsonian controls. Recordings from cortical slow-wave activity and global activation states were analysed separately. Rats with histologically confirmed xenografts showed behavioural improvement measured by counting apomorphine-induced rotations and with the extended body axis test. Firing rates in both nuclei were not significantly different between control and grafted groups. However, burst firing patterns in both nuclei in the slow-wave activity state were significantly reduced (P < 0.05) in rats with large surviving grafts, compared to hemiparkinsonian controls. The neuronal firing entropies and oscillations in both nuclei were restored to normal levels in the large-graft group. Electroencephalogram spike-triggered averages also showed normalization in the slow-wave activity state (P < 0.05). These results suggest that local continuous dopaminergic stimulation exerts a normalizing effect on the downstream parkinsonian basal ganglia firing patterns. This novel finding is relevant to future preclinical and clinical investigations of cell transplantation and the development of next-generation therapies for Parkinson's disease that ameliorate pathophysiological neural activity and provide optimal recovery of function.
doi:10.1093/brain/awr226
PMCID: PMC3212711  PMID: 21911417
neural transplantation; Parkinson's disease; substantia nigra pars reticulata; subthalamic nucleus; electrophysiology

Results 1-3 (3)