Glutamatergic Synapses On Ventral Tegmental Area Dopaminergic $ Excitability

Mesolimibic dopamine system is chiefly concerned with rewarding effects of dependence producing drugs and almost all the stimulative factors.Pre-research indicates that although function approachs of those stimulative factors are different,they all activate the MLDS,and enhance the activity of ventral tegmental area dopaminergic neurons.And then enhance the DA releasing size i7nstantaneously project to nucleus accumbens(Nac) and prefrontal cortex(pFC),and activate relative many encephalic regions, trigger animal direction and seek for rewarding stimulates.The mainly afferent fibers of the ventral tegmental area are the glutamatergic neuron afferents that from prefrontal cortex,amygdala and hippocampus.And it also receives cholinergic neuron afferents that from the midbrain laterodorsal tegmentum.From the in vivo research,we know that dopaminergic neurons will be induced to burst firing(this firing mode will enhance the DA releasing size instantaneously) from tonic firing when activating glutamatergic afferents because of excitatory amino acid or direct microiontophoretic application of glutamate.Also, if depresse the activity of ventral tegmental area by blocking glutamatergic afferents inputs.And then this will restrain the form of rewarding effect.These results prompt that that glutamatergic afferents inputs of ventral tegmental area can mediate the activity of dopaminergic neurons,and then influence the rewarding effect. In order to farther investigate the important influences of glutamatergic afferents to dopaminergic neurons,this article will introduce two parts works.The first is the infuence of high frequency stimulation on excitability of dopaminergic neurons in ventral tegmental area;second is the infuence of L-glutamate and carbachol on burst fring of dopaminergic neurons in ventral tegmental area.Firstly, the infuence of high frequency stimulation on excitability of dopaminergic neurons in ventral tegmental area.The presynaptic high frequency stimulation will induce long-term potentiation of dopaminergic neurons in ventral tegmental area in rat.But, whether the excitability of dopaminergic neurons in ventral tegmental area changed after high frequency stimulation has not previously been covered.The first part of this article we used perforated patch clamp technique in vitro to investigate the influence of presynaptic high frequency stimulation on excitability of dopaminergic neurons in ventral tegmental area.The experiment results showed that the rheobase of dopaminergic neurons decreased and the firing frequency increased after presynaptic high frequency stimulation(100HZ).From these results,we speculated that the excitability of dopaminergic neurons increased after high frequency stimulation.The second, the infuence of L-glutamate and carbachol on burst fring of dopaminergic neurons in ventral tegmental area. Burst firing of DA neurons induces a large transient increase in synaptic DA release and is considered to be the functionally relevant signal to encode rewarding effect.This firing mode is the core in the rewarding system.From the formerly research results,we know that burst firing of dopaminergic neurons in ventral tegmental area may need the synergistic action even coinstantaneous action of laterodorsal tegmentum and prefrontal cortex. But the mechanisms of burst generation of dopaminergic neuron still remain unclear.The second part of this article investigated the burst fring of VTA dopaminergic neurons in rat midbrain slices perfused with carbachol and L-glutamate individually or simultaneously to understand the neurotransmitter mechanism underlying burst generation. The results showed that bath application of carbachol and pulse application of L-glutamate both induced burst fring in dopaminergic neuron. Co-application of carbachol and L-glutamate induced burst fring in VTA dopaminergic cells which couldn't be induced to burst by the two chemicals separately. The result indicates that carbachol and L-glutamate co-regulate burst fring of dopaminergic neuron.