| The endocannabinoid(eCB) system is key system regulates many physiological processes including neurogenesis, axon guidance and synaptic plasticity throughout the central nervous system(CNS).The endocannabinoid system consists of several endogenous lipids, their target CB1 and CB2 receptors and enzymes responsible for their synthesis and degradation. ECBs, mainly include 2-arachidonoylglycerol(2-AG) and anandamide(AEA), regulates emotional and motivational states via activation of cannabinoid receptor 1(CB1R). The prefrontal cortex(PFC) and the limbic system with higher expression of CB1R, such as hippocampus, nucleus accumbens(NAc), cerebellum.which closely related to emotional, motivational and cognition responses. CB1-expressing neurons mainly include GABAergic and glutamatergic neurons, but expression of CB1 in glutamatergic neurons is low. Recent researches form Bradley D.Winters, reported on PNAS in 2012, show that CB1-expressing neurons within the NAc were exclusively fast-spiking interneurons(FSIs).The activation of CB1R and eCBs regulates synaptic plasticity in the glutamatergic neural circuit. The eCB-LTD has been reported in dorsal striatum, nucleus accumbens and hippocampus et al.. The nucleus accumbens(NAc), a key component in the mesolimbic dopamine system, functions to gate emotional and motivational responses. It is weightily to study the mechanism of the regulation to synaptic plasticity in the NAc.David Robbe reported their study results on NEUROBIOLOGY in 2002, which shows mechanism of the LFS-LTD evoked on PFC-NAc pathway. The initial steps of LTD induction is the activation of postsynaptic mGlu5R, with a rise in postsynaptic Ca2+, the retrograd signaling cascade led to postsynaptic eCB release and transport to presynaptic. The activaion of presynaptic CB1 receptors and activate the PKA, thereby promoting dephosphorylation of a presynaptic target that mediates a long-lasting reduction of transmitter release, the LTD evoked. This is a classical theory of eCB-LTD. However, whole-cell patch-clamp and extracellular field recordings were made from medium spiny neurons in parasagittal slices of mouse NAc by David Robbe. Whether the mechanism is sutied to in vivo recording is still not clear.To explore this question, in vivo field postsynaptic potentials(fEPSPs) induced by electric stimulating PFC-NAc projection fibers were recorded to evaluate the change on glutamaergic synaptic transmission in NAc shell through adult males C57 mice.Here we will introduce following parts of works:(1) The effects of acute AM281(i.p.),the antagonist of CB1R, on the LFS-LTD through in vivo recording. (2) The effects of acute picrotoxin(i.p.),the antagonist of GAB A A type receptor, at different time on the impact induced by AM281. (3) After blocked the GABAAR by picrotoxin, observe whether the CB1R-dependent LFS-LTD is exist in the PFC-NAc pathway in anesthetized animal, and inspect the effect of GABAAR on AM281 in NAc.The main results are as follows:(1) LFS-LTD can be induced on PFC-NAc neural pathway by electrical stimulation in anesthetized animal, but acute AM281(i.p.) not only fail to inhibit the LTD, but induce the decrease of the fEPSPs in NAc shell. Those results indicate that it is different from in vivo and in vitro recording, and the decrease of fEPSP evoked by AM281 give a prompt that there are other factors involved in.(2) The injection of PTX at different time, before the induction or after the producing of the decrease of fEPSPs evoked by AM281, both can inhibit the decrease, and make the fEPSPs increase. The result suggesting that the GABAA receptor may involved in the regulation of signal transduction in NAc in anesthetized animal.(3) After the acute injection of picrotoxin, LFS-LTD also can be recorded on the PFC-NAc neural pathway, but the injection of AM281 have no effect on the LFS-LTD induced without GABAA receptor. Compered with AM281-only treatment group, the effect on LFS-LTD is significantly different. The result suggesting that the regulate ability of AM281 in the NAc is associated with the GABAA receptor, and the result highlight the role of GABAergic synaptic transmission.In conclusion:first, compered with in vitro recording, in vivo electrophysiology recording emerged different signal transduction mechanism.second, in addition to the influence from glutamatergic pathway, the regulation of synaptic transmission in NAc should be influenced by fast spiking intemeurons(FSIs) which formed GABAergic synapses on medium spiny neurons(MSNs), providing feed-forward inhibition of NAc output in anesthetized animal. Moreover, there is an important reminder that the effect of eCB system may mediated by GABAergic pathway and in the NAc synaptic transmission, the role of GABAergic pathway seems more important. Those results provide important reference information for the research of the signal regulatory in NAc... |
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