Role of thalamic XXXX mediated by metabotropic @entity2227 receptor type 1 in @entity158 .

@entity32 @entity2227 @entity19 @entity406 @entity64294 @entity9830 @entity9446 @entity158 @entity38618
@entity64294 , one of the four isoforms of PLCbetas, is the sole isoform expressed in the @entity19 ventral posterolateral thalamic nucleus (VPL), a key station in @entity158 processing. The @entity19 thalamus also has been shown to express a high level of metabotropic @entity2227 receptor type 1 ( @entity9446 ), which stimulates PLCbetas through activation of Galphaq/11 protein. It is therefore expected that the thalamic @entity9446 -PLCbeta4 cascade may play a functional role in nociceptive transmission. To test this hypothesis, we first studied behavioral responses to various nociceptive stimuli in PLCbeta4 knock-out @entity19 . We performed the @entity406 test and found no difference in the @entity158 behavior in the first phase of the @entity406 test, which is attributed to acute nociception, between PLCbeta4 knock-out and wild-type @entity19 . Consistent with this result, acute @entity158 responses in the hot plate and tail flick tests were also unaffected in the PLCbeta4 knock-out @entity19 . However, the nociceptive behavior in the second phase of the @entity406 test, resulting from the tissue @entity32 , was attenuated in PLCbeta4 knock-out @entity19 . In the dorsal horn of the spinal cord where @entity38618 and PLCbeta4 mRNAs are expressed, no difference was found between the wild-type and knock-out @entity19 in the number of @entity9830 -like immunoreactive neurons, which represent neuronal activity in the second phase in the @entity406 test. Thus, it is unlikely that spinal PLCbeta4 is involved in the @entity406 -induced @entity158 . Next, we found that pretreatment with PLC inhibitors, @entity9446 antagonists, or both, by either intracerebroventricular or intrathalamic injection, attenuated the @entity406 -induced @entity158 behavior in the second phase in wild-type @entity19 . Furthermore, activation of @entity9446 at the VPL enhanced @entity158 behavior in the second phase in the wild-type @entity19 . In contrast, PLCbeta4 knock-out @entity19 did not show such enhancement, indicating that @entity9446 is connected to PLCbeta4 in the VPL. Finally, in parallel with the behavioral results, we showed in an electrophysiological study that the time course of firing discharges in VPL corresponds well to that of @entity158 behavior in the @entity406 test in both wild-type and PLCbeta4 knock-out @entity19 . These findings indicate that the thalamic @entity9446 -PLCbeta4 cascade is indispensable for the @entity406 -induced @entity158 by regulating the response of VPL neurons.
