Abstract
Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system.
Highlights
Prion protein ( PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show lateonset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl)
PrPC is highly expressed in normal cerebellar Purkinje cells (PCs) and granule c ells[11,12], indicating that the protein plays a role in normal cerebellar synaptic function and neuronal plasticity
We found that Ngsk Prnp0/0 mice showed weakened GABAA-mediated inhibitory postsynaptic currents in PCs and impaired long-term depression (LTD), suggesting that PrPLP/Dpl expression can induce cerebellar dysfunctions by impairing cerebellar synaptic transmission
Summary
Prion protein ( PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show lateonset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred This electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. In the present study, we examined whether a deficiency in P rPC and ectopic expression of PrPLP/Dpl in Ngsk Prnp0/0 mice affect cerebellar physiological functions by evaluating the basic excitatory and inhibitory synaptic transmission to PCs and long-term depression (LTD) of excitatory synaptic transmission at parallel fibre (PF)-PC synapses. We found that Ngsk Prnp0/0 mice showed weakened GABAA-mediated inhibitory postsynaptic currents in PCs and impaired LTD, suggesting that PrPLP/Dpl expression can induce cerebellar dysfunctions by impairing cerebellar synaptic transmission
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