Abstract
BackgroundLurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration.ResultsWe observed a specific reduction in γ2 subunit gene expression, while α1–5, β1–2, γ1,3 and δ subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the γ2 down-regulation was present only after the onset of degeneration at p14. The difference in γ2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice.ConclusionIn conclusion, the down-regulation of γ2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.
Highlights
Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks
In conclusion, the down-regulation of γ2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of deep cerebellar nuclei (DCN) tissue to massive GABAergic deafferentation
Using real-time RT-PCR, mRNA expression levels of GABAA receptor subunits α1–5, β1–2, γ1–3 and δ were investigated in tissue of DCN obtained from Lurcher mutants aged p11 and p14 and compared to wild type
Summary
Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Inhibitory projections are sometimes placed at decisive locations within the motor system and are important for programming and controlling the execution of movement One of these projections is the GABAergic Purkinje cell (PC) projection onto the deep cerebellar nuclei (DCN) neurons. This projection system undergoes a degeneration in the spontaneous, autosomal semidominant mouse mutation Lurcher, yielding nonviable homozygous mice, while heterozygous individuals (Lc/+) show ataxia expressed by a tendency to fall [1]. The majority of DCN neurons survive, albeit deprived of their inhibitory PC input [8,9]
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