Research Paper Volume 13, Issue 16 pp 20319—20334

Inhibition of endoplasmic reticulum stress reverses synaptic plasticity deficits in striatum of DYT1 dystonia mice

Altered striatal long-term synaptic plasticity in Tor1a+/- mice. (A) Time-course of striatal LTD expression in SPNs from Tor1a+/+ and Tor1a+/- mice. HFS protocol induced LTD in SPNs recorded from Tor1a+/+ mice (P+/- mice (P>0.05). (B) Time-course of striatal LTP expression in SPNs from Tor1a+/+ and Tor1a+/- mice. In Tor1a+/- SPNs LTP showed a tendency to increase compared with wild-type SPNs. (C) Summary plot of NMDA/AMPA current ratio calculated in SPNs from Tor1a+/+ and Tor1a+/- mice. A significant decrease of NMDA/AMPA ratio was detected in Tor1a+/- mice, compared to Tor1a+/+ mice. (D) AMPAR-mediated currents recorded at different HP in Tor1a+/+ and Tor1a+/- SPNs. The I-V relationship showed a significant increase in the current recorded at more hyperpolarized range from Tor1a+/- SPNs (HP= -70 mV, PE) Normalized IV relationships of NMDAR-mediated currents showed no difference between genotypes (P >0.05). In each group, five mice were used (N=5), and three independent electrophysiological recordings were conducted for each mouse (n=3). P

Figure 1. Altered striatal long-term synaptic plasticity in Tor1a+/- mice. (A) Time-course of striatal LTD expression in SPNs from Tor1a+/+ and Tor1a+/- mice. HFS protocol induced LTD in SPNs recorded from Tor1a+/+ mice (P<0.05), but not from Tor1a+/- mice (P>0.05). (B) Time-course of striatal LTP expression in SPNs from Tor1a+/+ and Tor1a+/- mice. In Tor1a+/- SPNs LTP showed a tendency to increase compared with wild-type SPNs. (C) Summary plot of NMDA/AMPA current ratio calculated in SPNs from Tor1a+/+ and Tor1a+/- mice. A significant decrease of NMDA/AMPA ratio was detected in Tor1a+/- mice, compared to Tor1a+/+ mice. (D) AMPAR-mediated currents recorded at different HP in Tor1a+/+ and Tor1a+/- SPNs. The I-V relationship showed a significant increase in the current recorded at more hyperpolarized range from Tor1a+/- SPNs (HP= -70 mV, P<0.01). (E) Normalized IV relationships of NMDAR-mediated currents showed no difference between genotypes (P >0.05). In each group, five mice were used (N=5), and three independent electrophysiological recordings were conducted for each mouse (n=3). P<0.05 was considered to be statistically significant.