Synaptic transmission and synaptic plasticity in the mouse striatum

Abstract: The striatum is the major input nucleus of the basal ganglia and can be subdivided into a dorsal part and a ventral part that is also named nucleus accumbens (NAc). The dorsal part is involved in motor control and habit learning whereas the ventral part is mostly associated with rewardmotivated behaviors. The neurons that populate the striatum are for 95% GABAergic medium spiny neurons. Input into the striatum comes from cortex and thalamus and is mostly glutamatergic. This glutamatergic input is the essential drive behind excitatory synaptic transmission in the striatum. Apart from glutamatergic input, the striatum also receives dopaminergic input from the midbrain. To measure excitatory synaptic transmission and synaptic plasticity we used field potential recordings which measures the activity of a population of neurons in the striatum evoked by stimulation of glutamatergic fibers. In order to study the involvement of specific neurotransmitters and receptors involved in synaptic transmission and its modulation, we applied pharmacological tools in the perfusion solution that modify glutamatergic, dopaminergic and GABAergic synaptic transmission. We also measured the levels of the neuromodulator dopamine which plays an important part in striatal synaptic transmission. In order to study long term potentiation (LTP), we applied a high frequency stimulation-protocol. We found that glutamatergic synaptic transmission in the striatum is depressed by bathapplication of N-methyl-D-aspartate (NMDA). We found that this depression is mediated by adenosine acting on A1-receptors. The NMDA-receptors that mediate this depression were shown to contain the NR1/NR2A-subnunits. These NMDA-receptors are most likely located in the striatum on medium spiny neurons. Furthermore, bath-applied NMDA also depresses evoked dopamine-release in striatum via NMDA-receptors that contain NR1/NR2A-subunits. LTP in the NAc was shown to be independent of the Mg2+-block of NMDA receptors but rather depends on the level of NMDA-receptor activation. We also showed that LTP depends on dopamine D1- but not D2-receptors, is independent of GABA-receptor activation but requires the activation of group I mGluRs. Finally, we showed differences in neuronal excitability in the striatum and NAc between male and female mice in different stages of the estrous cycle. In addition, the excitability of striatal neurons of both male and female mice is modulated by acute administration of estrogen. Together, these results contribute to understanding the role of different neurotransmitters in the physiology of the striatum.