Synapse
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Using mice with a targeted disruption of the adenosine A1 receptor (A1R), we examined the role of A1Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A1 receptor knockout (A1R-/-), heterozygote (A1R+/-), and wildtype (A1R+/+) mice. However, paired pulse facilitation was impaired significantly in A1R-/- slices as compared to A1R+/+ slices. ⋯ However, 10 months later A1R-/- mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine A1R knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model.
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The effect of the premature commitment of neurons to exuberant growth by nicotine on concurrent and subsequent learning is unknown and was the focus of the present study. Animals were trained on a tray reaching for food task (where lots of pieces of chicken feed were available) for 3 weeks before they received two daily injections of nicotine (0.3 mg/kg) or 0.9% saline for 12 days. Measures of tray-reaching performance were obtained before the administration of nicotine and every other week for a total of 7 weeks. ⋯ In contrast, animals treated with nicotine showed bilateral increases in neuronal branching. Behavioral results showed that nicotine improved forelimb use in the concurrently administered tray-reaching task, but severely degraded quantitative and qualitative scores of skilled forelimb use in the subsequently administered single-pellet reaching task. The results suggest that plasticity coincidence with skilled training is essential to skilled motor learning, but this expenditure can impair subsequent learning.
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Unilateral damage to the forelimb representation area of the sensorimotor cortex (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the lesion) forelimb as well as reorganization of neuronal structure and connectivity in the contralateral motor cortex. Recently, male rats with unilateral electrolytic SMC lesions were found to have enhanced skilled reaching performance with the ipsilesional forelimb compared with sham-operated controls. The present study was performed to determine whether these behavioral findings are replicable using an ischemic lesion and whether there is a link between the enhanced learning and synaptogenesis in motor cortical layer V opposite the trained limb and lesion, as assessed using stereological methods for light and electron microscopy. ⋯ Lesions, but not training, significantly increased the total number of motor cortical layer V synapses per neuron as well as the number of perforated and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in addition to a net increase in synapses, the improved reaching ability was coupled with an increase in synapse subtypes that have previously been linked to enhanced synaptic efficacy. The failure to induce synaptogenesis in layer V with reach training alone is in contrast to previous findings and may be related to training intensity.
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Opioid abuse is associated with repeated administration and escalation of dose that can result in profound adaptations in homeostatic processes. Potential cellular mechanisms and neural sites mediating opiate-dependent adaptations may involve NMDA-dependent synaptic plasticity within brain areas participating in behaviors related to consumption of natural reinforcers, as well as affective-autonomic integration, notably the medial nucleus tractus solitarius (mNTS). NMDA-dependent synaptic plasticity may be mediated by changes in the intracellular and surface targeting of NMDA receptors, particularly in postsynaptic sites including spines or small distal dendrites. ⋯ Collapsed across all NR1-labeled dendrites, rats self-administering morphine had a lower number of plasmalemmal gold particles per unit surface area (7.1 +/- 0.8 vs. 14.4 +/- 1 per 100 microm), but had a higher number of intracellular gold particles per unit cross-sectional area (169 +/- 6.1 vs. 148 +/- 5.1 per 100 microm2) compared to saline self-administering rats. Morphometric analysis showed that the decrease in plasma membrane labeling of NR1 was most robust in small dendritic profiles (<1 microm), where there was a reciprocal increase in the density of intracellular particles. These results indicate that the plasmalemmal distribution of the essential NR1 subunits in distal sites may prominently contribute to NMDA receptor-dependent modulation of neural circuitry regulating homeostatic processes, and targeting of these proteins can be prominently affected by morphine self-administration.
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Comparative Study
Lesion of subthalamic or motor thalamic nucleus in 6-hydroxydopamine-treated rats: effects on striatal glutamate and apomorphine-induced contralateral rotations.
A unilateral lesion of the rat nigrostriatal pathway with 6-hydroxydopamine (6-OHDA) results in a decrease in the basal extracellular level of striatal glutamate, a nearly complete loss of tyrosine hydroxylase (TH) immunolabeling, an increase in the density of glutamate immunogold labeling within nerve terminals making an asymmetrical synaptic contact, and an increase in the number of apomorphine-induced contralateral rotations. [Meshul et al. (1999) Neuroscience 88:1-16; Meshul and Allen (2000) Synapse 36:129-142]. In Parkinson's disease, a lesion of either the subthalamic nucleus (STN) or the motor thalamic nucleus relieves the patient of some of the motor difficulties associated with this disorder. In this rodent model, either the STN or motor thalamic nucleus was electrolytically destroyed 2 months following a unilateral 6-OHDA lesions. ⋯ There was no change in nerve terminal glutamate immunogold labeling in either the motor thalamic or motor thalamic plus 6-OHDA lesion groups compared to the sham group. The decrease in the number of apomorphine-induced rotations was not due to an increase in TH immunolabeling (i.e., sprouting) within the denervated striatum. This suggests that alterations in striatal glutamate appear not to be directly involved in the STN or motor thalamic lesion-induced reduction in contralateral rotations.