Dopamine-Dependent Synaptic Plasticity in the Striatal Cholinergic Interneurons

Abstract

The striatum, the input stage of the basal ganglia, is a critical brain structure for the learning of stimulus-response habits as well as motor, perceptual, and cognitive skills. Roles of dopamine (DA) and acetylcholine (ACh) in this form of implicit memory have long been considered essential, but the underlying cellular mechanism is still unclear. By means of patch-clamp recordings from corticostriatal slices of the mouse, we studied whether the identified striatal cholinergic interneurons undergo long-term synaptic changes after tetanic stimulation of corticoand thalamostriatal fibers. Electrical stimulation of the fibers revealed a depolarizing and hyperpolarizing postsynaptic potential in the striatal cholinergic interneurons. The early depolarizing phase was considered to be a cortico/thalamostriatal glutamatergic EPSP, and the hyperpolarizing component was considered to be an intrastriatally evoked GABAergic IPSP. Tetanic stimulation of cortico/thalamostriatal fibers was found to induce simultaneously occurring long-term potentiation (LTP) of the EPSPs as well as the disynaptically mediated IPSPs. The induction of LTP of EPSP required a rise in intracellular Ca 2ϩ concentration and dopamine D 5 , but not D 2 receptor activation. Ca 2ϩ -permeable AMPA receptors might also play a part in the LTP induction. Blockade of NMDA receptors, metabotropic glutamate receptors, or serotonin receptors had no significant effects. The long-term enhancement of the disynaptic IPSPs was caused by a long-term increase in the occurrence rate but not the amplitude of disynaptically mediated IPSP in the striatal cholinergic interneurons. This dual mechanism of synaptic plasticity may be responsible for the long-term modulation of the cortico/thalamostriatal synaptic transmission.

Dopamine and cyclic-AMP regulated phosphoprotein-32–dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons

“…Thus, a D2-selective attenuation of feedforward inhibitory neuron input to cholinergic neurons was observed in WT, but not KO, slices. This is consistent with D2-like presynaptic suppression of cortically-evoked IPSPs reported in rat striatal cholinergic neurons (Pisani et al, 2000;Suzuki et al, 2001;Centonze et al, 2003). …”

“…Although cortical stimulation did not produce prominent excitation (EPSPs) in WT cholinergic-like neurons, in part due to their depolarized membrane potentials, corticallyevoked disynaptic IPSPs were readily observed, and D2-like receptor stimulation potently attenuated the evoked IPSPs in these neurons. This is consistent with studies in the rat dorsal striatum showing that D2 agonists inhibit local GABA release and reduces spontaneous and evoked disynaptic inhibitory potentials in striatal cholinergic neurons (Suzuki et al, 2001;Centonze et al, 2003) via a D2 presynaptic mechanism (Pisani et al, 2005 Aizman et al, 2000) that could account for the observed D2-mediated attenuation of GABAergic IPSPs in WT cholinergic-like neurons. However, FS interneurons do not express DARPP-32 proteins .…”

“…Therefore, the ability of tonic D1/D5 stimulation to increase (maintain) the EPSPs evoked by cortical stimulation was absent in FS neurons in KO brain slices ( Figure 4D). Thus, in contrast to an inhibitory D2/D4 receptor regulation of cortical input to WT spiny neurons ( Figure 2D1), a tonic D1/ D5-mediated enhancement in cortical-evoked EPSPs was observed in aspiny FS neurons of WT but not KO mouse slices.Cholinergic-like Interneurons-Nineteen (13 WT and 6 KO) accumbens neurons were recorded that exhibited characteristics consistent with those described for striatal cholinergic interneurons (Aosaki et al, 1998;Pisani et al, 2000;Suzuki et al, 2001). These large-sized interneurons ( Figure 3A1-5) had 1-2 thick primary dendrites that branch into fine processes and had a significantly more depolarized membrane potential (−60.8 ±1.3 mV) and higher input resistance (151.6 ± 58.0 MΩ) than medium-sized aspiny fast spiking (FS) and spiny GABA neurons ( Figure 3D).…”

“…Secondly, cortically-evoked synaptic responses were examined in accumbens neurons of WT and KO mouse slices. The effects of DA D1-and D2-like receptor agonists and antagonists were examined in identified NAC spiny neurons and aspiny interneurons with fast spiking or cholinergic-like characteristics, which have been well characterized in the dorsal striatum (Aosaki et al, 1998;Koos and Tepper, 1999;Pisani et al, 2000;Bracci et al, 2001;Suzuki et al, 2001;Centonze et al, 2003;Tepper et al, 2004) but have not yet been studied in the NAC of rats or mice. Portions of these data were presented in abstract form (Onn et al, 2006b).…”

Activation of Muscarinic and Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Core Is Necessary for the Acquisition of Drug Reinforcement

“…Local intra-NACore antagonism of mAchRs or nAChRs completely and reversibly blocked the acquisition of RMF reinforcement, indicating (1) that activation of both mAchR and nAChR in the NACore is necessary for the conditioning of the positive reinforcing effect of RMF (i.e., for the animal's learning to associate the drug stimulus with the appropriate operant response) and (2) that the ACh release by cholinergic large aspiny interneurons, the second most prevalent neuron population in the striatum including the NACore (Squire et al, 2003), is instrumental for this learning process. Thus, the general rule that striatal cholinergic interneurons play an eminent role in the formation of stimulus-response associations (i.e., learning) (Aosaki et al, 1994;Calabresi et al, 2000;Suzuki et al, 2001;Kitabatake et al, 2003;Mansvelder et al, 2005) also seems to apply to the NACore, a striatal structure dedicated to processing stimuli of high emotional and motivational valence (Haber et al, 1985;Jongen-Relo et al, 1994). Striatal cholinergic interneurons are known to affect GABAergic medium spiny neurons, which constitute the major (95%) neuron population of the striatum and also serve as the major motivational/locomotor output of the striatum (Haber et al, 1985;Heimer et al, 1991;Zahm and Brog, 1992;Meredith and Chang, 1994;Squire et al, 2003;Voorn et al, 2004).…”