Cerebellar LTD and learning-dependent timing of conditioned eyelid responses.

Mammals can be trained to make a conditioned movement at a precise time, which is correlated to the interval between the conditioned stimulus and unconditioned stimulus during the learning. This learning-dependent timing has been shown to depend on an intact cerebellar cortex, but which cellular process is responsible for this form of learning remains to be demonstrated. Here, we show that protein kinase C-dependent long-term depression in Purkinje cells is necessary for learning-dependent timing of Pavlovian-conditioned eyeblink responses.

Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression.

The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is characterized by the absence of both mossy fiber long-term potentiation and long-term depression. This mutant was backcrossed to 129S3/SvImJ and C57Bl/6J to obtain standardized genetic backgrounds. Spatial working memory, assessed in the eight-arm radial maze, was unchanged in rab3A null-mutants. Moreover, one-trial cued and contextual fear conditioning was normal. Long-term spatial memory was tested in the Morris water maze. Two different versions of this task were used, an 'easy' version and a 'difficult' one. On both versions, no differences in search time and quadrant preferences were observed. Thus, despite the elimination of mossy fiber long-term plasticity, these tests revealed no impairments in mnemonic capabilities. We conclude that spatial, contextual and working memory do not depend on mossy fiber plasticity.

Muscarinic acetylcholine receptor immunoreactivity in the amygdala--II. Fear-induced plasticity.

Changes in the distribution of muscarinic acetylcholine receptor-immunoreactive neurons were examined in the amygdaloid complex at different time-intervals following a single training session of active shock avoidance in a two-way shuttle-box. Muscarinic acetylcholine receptors were visualized using M35, a monoclonal antibody raised against purified muscarinic acetylcholine receptor protein. Both in naive animals and 2 h after active shock avoidance training, muscarinic acetylcholine receptor immunoreactivity was high in the central nucleus, and only low to moderate in other amygdaloid regions. Twenty-four hours after training, however, the muscarinic acetylcholine receptor immunoreactivity distribution pattern was reversed, showing a dramatic increase in the corticomedial nucleus, while in contrast, in other amygdaloid regions including the central nucleus, muscarinic acetylcholine receptor immunoreactivity was reduced to only a few scattered neurons. Additional studies with a modified experimental design indicated that fear conditioning mechanisms in association with the severity of the aversive stimuli, and not the learning of the avoidance response, may account for the changes in muscarinic acetylcholine receptor immunoreactivity in the amygdala. These results are consistent with the prominent role of the central nucleus in the conditioning and expression of the fear response. A closer examination revealed that 8 h after training the changes in both the central and corticomedial nuclei became significant. The differences still existed after 25 days, but three months after the training session the receptor distribution was returned to normal. The long-lasting, but reversible nature of these changes indicates that fear conditioning is accompanied by a dynamic plasticity of muscarinic acetylcholine receptor immunoreactivity in the amygdaloid complex.

Y chromosomal effects on hippocampal mossy fiber distributions in mice selected for aggression.

The influence of the non-pseudoautosomal region of the Y chromosome (YNPAR) on the sizes of the hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields were examined in wild house mice. For this purpose selection lines for short attack latency (SAL), long attack latency (LAL), and their respective congenics for the YNPAR were used. We found an incremental effect of the (non-aggressive) LAL YNPAR, combined with an additive effect of the line background on the sizes of the IIPMF terminal fields. In contrast, only the line background affected attack latency. The implications of this finding for the previously observed correlation between the size of the IIPMF and aggression in male house mice are discussed.