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SV2C is an isoform of the synaptic vesicle 2 protein family that exhibits a particular pattern of brain expression with enriched expression in several basal ganglia nuclei. In the present study, we have investigated SV2C implication in both normal and pathological basal ganglia functioning with a peculiar attention to dopamine neuron containing regions. In SV2C-/- mice, the expression of tyrosine hydroxylase mRNA in midbrain dopaminergic neurons was largely and significantly increased and enkephalin mRNA expression was significantly decreased in the caudate-putamen and accumbens nucleus. The expression of SV2C was studied in two models of dopaminergic denervation (6-OHDA- and MPTP-induced lesions). In dopamine-depleted animals, SV2C mRNA expression was significant increased in the striatum. In order to further understand the role of SV2C, we performed behavioral experiments on SV2C-/- mice and on knock-down mice receiving an injection of adeno-associated virus expressing SV2C miRNA specifically in the ventral midbrain. These modifications of SV2C expression had little or no impact on behavior in open field and elevated plus maze. However, even if complete loss of SV2C had no impact on conditioned place preference induced by cocaine, the specific knock-down of SV2C expression in the dopaminergic neurons completely abolished the development of a CPP while the reaction to an acute drug injection remains similar in these mice compared to control mice. These results showed that SV2C, a poorly functionally characterized protein is strongly involved in normal operation of the basal ganglia network and could be also involved in system adaptation in basal ganglia pathological conditions.

This study provides evidences strongly suggesting that PD-like lesion and L-dopa therapy were concomitant factors involved in striatal remodeling underlying the pramipexole-induced place preference. Molecular and pharmacological data suggest a key involvement of the glutamatergic pathway in this behavioral outcome.

When an odor is paired with a delayed illness, rats acquire a relatively weak odor aversion. In contrast, rats develop a strong aversion to an olfactory cue paired with delayed illness if it is presented simultaneously with a gustatory cue. Such a conditioning effect has been referred to as taste-potentiated odor aversion learning (TPOA). TPOA is an interesting model for studying neural mechanisms of plasticity because of its robustness and rapid acquisition. However, the neural substrate involved in TPOA retrieval has not been well characterized. To address this question, we used immunocytochemical detection of inducible transcription factors encoded by the immediate-early genes Fos and Egr1. Thirsty male rats were conditioned to TPOA learning, and they were submitted to retrieval in the presence of the learned odor 3 d later. Significant increases in both Fos and Egr1 expressions were observed in basolateral amygdala, insular cortex, and hippocampus in aversive rats in comparison with the all the control groups. The pattern of neuronal activity seemed unlikely to be related to the sole LiCl injection. Lastly, opposite patterns of Fos and Egr1 were noted in the entorhinal cortex and the central nucleus of amygdala, suggesting a differential involvement of these markers in retrieval of TPOA.Odors are critical cues for rodents since odors give the rodents information about their environment. Odors allow the rodents to escape from predators, to find food, or to avoid consumption of toxic products. Memorization of such information is crucial for animal survival. Moreover, olfactory learning permits a previously neutral cue to acquire significance after having been paired with a biologically relevant reinforcement. Rats can acquire weak aversion when an odor is paired with delayed-illness (Bernstein 1991). In contrast, when an odor is simultaneously presented with a taste cue, rats can develop strong aversion to the odor cue. Such a conditioning has been referred to as tastepotentiated odor aversion (TPOA) learning (Palmerino et al. 1980). Thus, taste-mediated potentiation allows odor to gain associative strength and the animals to avoid consumption of poisonous substance on the basis of its odor only (Bernstein 1991). TPOA learning is an attractive model for studying odor memory because of its robustness, rapid acquisition, and adaptive feature (Welzl et al. 2001).Most of the data regarding the brain areas that could mediate TPOA learning are provided by either lesion or pharmalogical experiments. Various brains areas involved in olfactory, gustatory, and visceral pain processing could play a role in TPOA learning. Several studies (Bermùdez-Rattoni et al. 1986;Hatfield et al. 1992;Ferry et al. 1995) indicate that the basolateral nucleus of amygdala (BLA) could play a major role in the acquisition but not in the retrieval of TPOA. In addition, the BLA is known for its involvement in learning the biological significance of events and could modulate memory storage of emotional events (McGaugh 2002). In contrast, the l...

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