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Single-unit activity in the striatum of unrestrained, conscious rats was characterized by extracellular recording in combination with iontophoresis. To avoid the confounding effect of motor-related changes in firing rate, measurements were restricted to periods when animals were at quiet rest. Recording electrodes were lowered stepwise through 4.0 mm of anterior striatum in 36 equal ventral movements of 111 microm to assess the ratio of spontaneously active vs. silent neurons. Spontaneous activity was assessed at each step followed by iontophoretic glutamate (GLU) application to expose silent neurons. Eleven such experimental sessions resulted in a total of 100 spontaneously active and 264 silent neurons, indicating that without overt movement the large majority (72.7%) of striatal cells are silent. Spontaneously active neurons, moreover, discharged at low rates (4.85 +/- 0.85 spikes/s). In separate experiments, both the AMPA/kainate (CNQX: 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline disodium salt) and NMDA (AP5: D-(-)-2-amino-5-phosphonovaleric acid) GLU-receptor antagonists blocked the activity of most spontaneously active (83% CNQX, 69% AP5), and GLU-stimulated silent (68% CNQX, 98% AP5) units. Collectively, our results are consistent with an overall low level of striatal activity in the absence of strong excitatory input. When neuronal activity is initiated, however, it appears that both NMDA and AMPA/kainate receptors are critical for maintaining continuous impulse activity.

Background: A physiological increase in extracellular ascorbate (AA), an antioxidant vitamin found throughout the striatum, elevates extracellular glutamate (GLU). To determine the role of behavioral arousal in this interaction, microdialysis was used to measure striatal GLU efflux in rats tested in either a lights-off or lights-on condition while reverse dialysis either maintained the concentration of AA at 250 µM or increased it to 1000 µM to approximate endogenous changes.

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.

The interest in using neurotrophic factors as potential treatments for neurodegenerative disorders, such as Huntington's disease, has grown in the past decade. A major impediment for the clinical utility of neurotrophic factors is their inability to cross the blood-brain barrier in therapeutically significant amounts. Although several novel mechanisms for delivering exogenous neurotrophins to the brain have been developed, most of them involve invasive procedures or present significant risks. One approach to circumventing these problems is using therapeutic agents that can be administered systemically and have the ability to enhance the activity of neurotrophic factors. This review highlights the use of gangliosides, substituted pyrimidines, and mesenchymal stem cells as neurotrophic enhancers that have significant therapeutic potential while avoiding the pitfalls of delivering exogenous neurotrophic factors through the blood-brain barrier. The review focuses on the potential of these neurotrophic enhancers for treating the behavioral deficits in rodent models of Huntington's disease.

These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs may be a viable treatment for stroke-induced cognitive dysfunction.

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD.