The Effects Of Endogenous Dopamine On Short Term Plasticity Of Corticostrital Sysnapses In Acute Brain Slices

ObjectiveTo investigate the effects of endogenous dopamine (DA) on striatum medium spiny neurons(MSNs) in acute brain slices by the means of electrophysiology, and in an attempt to clarify the impact of the nigrostriatal circuit loop on the functional status of the MSNs.MethodsWe established the acute corticostriatonigral slices to observe the basic electrophysiological activity with the visual patch clamp whole-cell recording technique on acute brain slices.With the various kinds of the structures combination which consist of striatum and cortex or/and substantia nigra, we explored the conditions with appearance of the spontaneous two-state voltage oscillations. Then, with the methods of blocking the dopaminergic or glutamic acid receptor respectively, we inverstigated how the aminoglutaminic acid, which was come from the cortex, and the dopamine, which was from substantia nigra, made affects on the two-state voltage oscillations.Recording the excitatory postsynaptic current(EPSC) of MSNs in dorsal striatum while performing paired pulses or short train pulses to the cortex, to oberserve the change in short term plasticity. Observing the effect of dopamine on the short term plasticity by blocking the dopamine receptors in the corticostritonigral slice.Results1. Substantia nigral neurons displayed characteristical spontaneous action potentials and hyperpolarization-activated inward current in corticostriatonigral slices. They were consistent with the characteristics of dopaminergic neurons orγ-aminobutyric acid neurons in vivo. Spontaneous two-state voltage oscillations were recorded in some striatal medium spiny neurons as they were in vivo.2. 65.2 %( 30/46) MSNs recorded in corticostriatonigral slices displayed spontaneous two-state voltage oscillations. 92.3% (24/26) of MSNs in the dorsal striatum near to the cortex, only 30% of MSNs in the ventral striatum. The amplitude of depolarized plateau potential(up state) were decreased by blocking dopamine receptors (P <0.05). The potential level of up state was reduced by blocking D1 receptors (P <0.05), action potentials were stopped. The results of blocking D2 receptors were the potentials level of two states raised (P<0.05). MSNs membrane potential showed a stable resting level in any slice of corticostriatal slice(-67.3±2.7mV, n=10), striatal slice (-73.2±3.3mV, n=10) and nigrostriatal slice (-71.4±2.5mV,n=10). There was no significant difference(P >0.05).3. Compared the PPR in corticostriatonigral slices with it in corticostriatal slices, there was significant difference in PPR(50ms ISI:139.6±18.2% / 113.3±13.7%, P<0.01; 500ms ISI 67.4±10.6% /83.1±5.9% P<0.01). PPR before and after blocking the D2 receptors in corticostriatonigral slices was(50ms ISI:136.5±12.6% / 113.6±10.5%,P<0.01;500ms ISI:66.2±6.4% / 79.3±7.1%,P<0.01). there was no significant difference compared PPR in corticostriatonigral slices after blocking the D2 receptors with PPR in corticostriatal slices(P>0.05). 20 stimuli delivered at 10 Hz could induce the decrease of the EPSC amplitude, which showed STD. The STD ratio in corticostriatonigral slices was(0.20±0.03), The STD ratio increased after blocking the D1 receptors (0.58±0.03,P<0.001), the extent of STD decreased. The D2 receptors have no effect on the STD ratio. 20 stimuli delivered at 10 Hz could change the EPSC in corticostriatal slices as in corticostriatonigral slices. The STD ratio(0.59±0.05) increased than it in corticostriatonigral slices(P<0.001). But comparing with the STD ratio in the in corticostriatonigral slices after blocking the D1 receptors, there was no significant difference(P>0.05). Conclusions1. Substantia nigral neurons and striatal neurons in saggital brain slice keep the basic electrophysiological activity as in vivo.2. Spontaneous two-state voltage oscillations in striatal medium spiny neurons are the results of MSN receiving the afferent of cortical glutamatergic excitatory afferent and the regulation of dopamine. Reflecting the whole circuits between the striatum and cortex, substantia nigra neurons.3. Endogenous Dopamine from the substantia nigra maybe regulate the instantaneous integration and coding of MSNs to the information from the cortex by tonic effect on the short term plasticity of paired pulses and short train pulses in the corticostriatal synapses.