Dopamine Receptor–Mediated Mechanisms Involved in the Expression of Learned Activity of Primate Striatal Neurons

Abstract

To understand the mechanisms by which basal ganglia neurons express acquired activities during and after behavioral learning, selective dopamine (DA) receptor antagonists were applied while recording the activity of striatal neurons in monkeys performing behavioral tasks. In experiment 1, a monkey was trained to associate a click sound with a drop of reward water. DA receptor antagonists were administered by micropressure using a stainless steel injection cannula (300 microm ID) through which a Teflon-coated tungsten wire for recording neuronal activity had been threaded. Responses to sound by tonically active neurons (TANs), a class of neurons in the primate striatum, were recorded through a tungsten wire electrode during the application of either D1- or D2-class DA receptor antagonists (total volume <1 microl, at a rate of 1 microl/5-10 min). Application of the D2-class antagonist, (-)-sulpiride (20 micrograms/microl, 58 mM, pH 6.8), abolished the responses of four of five TANs examined. In another five TANs, neither the D2-class antagonist nor the D1-class antagonists, SCH23390 (10 micrograms/microl, 31 mM, pH 5.7) or cis-flupenthixol (30 micrograms/microl, 59 mM, pH 6.6) significantly suppressed responses. In experiment 2, four- or five-barreled glass microelectrodes were inserted into the striatum. The central barrel was used for extracellular recording of activity of TANs. Each DA receptor antagonist was iontophoretically applied through one of the surrounding barrels. SCH23390 (10 mM, pH 4.5) and (-)-sulpiride (10 mM, pH 4.5) were used. The effects of iontophoresis of both D1- and D2-class antagonists were examined in 40 TANs. Of 40 TANs from which recordings were made, responses were suppressed exclusively by the D2-class antagonist in 19 TANs, exclusively by the D1-class antagonist in 3 TANs, and by both D1- and D2-class antagonists in 7 TANs. When 0.9% NaCl, saline, was applied by pressure (<1 microl) or by iontophoresis (<30 nA) as a control, neither the background discharge rates nor the responses of TANs were significantly influenced. Background discharge rate of TANs was also not affected by D1- or D2-class antagonists applied by either micropressure injection or iontophoresis. It was concluded that the nigrostriatal DA system enables TANs to express learned activity primarily through D2-class and partly through D1-class receptor-mediated mechanisms in the striatum.

Involvement ofIhin Dopamine Modulation of Tonic Firing in Striatal Cholinergic Interneurons

“…These data further support that the sAHP after driven activity may underlie the pause responses in cholinergic interneurons (Reynolds et al, 2004;Wilson and Goldberg, 2006). Dopaminergic activity is involved in the pause response (Aosaki et al, 1994a,b;Watanabe and Kimura, 1998), presumably by potentiating excitatory synaptic inputs that increase sAHP amplitude (Reynolds et al, 2004). However, synaptic inputs can be amplified by intrinsic membrane conductances (Wilson, 2005), raising a possibility that dopaminergic modulation of these conductances may also contribute to the pause response.…”

“…Recordings of cholinergic interneurons in vivo (Wilson et al, 1990;Reynolds et al, 2004) and in vitro (Jiang and North, 1991;Bennett and Wilson, 1999;Goldberg and Wilson, 2005;Wilson, 2005) have revealed that these cells correspond to the tonically active neurons (TANs) in the striatum. The TANs exhibit pauses in tonic firing in response to salient stimuli during associative learning (Aosaki et al, 1994a,b;Apicella, 2002;Morris et al, 2004), which are dependent on dopaminergic inputs from the substantia nigra (Aosaki et al, 1994a;Watanabe and Kimura, 1998). However, the cellular mechanisms underlying the pause response are still unclear.…”

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys

“…With respect to motivational aspects of PR performance, studies show that nigro-striatal dopaminergic projections (Ljungberg et al 1991;Schultz et al 1993a;Schultz et al 1993b) and D 2 -expressing cholinergic interneurons (Watanabe and Kimura 1998) may encode motivation and reward value in a plastic manner. In particular Watanabe and colleagues show that learned, reward-associated alterations in striatal neuron discharge rates are attenuated by local application of both D 1 -like and D 2 -like antagonists (Watanabe and Kimura 1998). Thus, it is likely that both the D 1 -like and D 2 -like antagonist effects on PR performance are likely to be specific for motivational aspects of the task.…”

Role of Dopamine in the Primate Caudate Nucleus in Reward Modulation of Saccades

“…The drug solution was pressure-injected, 0.2 l every 30 s for 10 times, for a total of 2 l. We used ((R)-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (SCH23390; 8 g/l) as a dopamine D 1 antagonist and Eticlopride hydrochloride (6 g/l) as a dopamine D 2 antagonist (Sigma, St. Louis, MO), both directly dissolved by saline. These doses were chosen based on the previous reports (Watanabe and Kimura, 1998;Bari and Pierce, 2005). We also injected saline as a separate experiment to ensure the effect was not caused by any mechanical effect by liquid injection (data are in supplemental material, available at www.jneurosci.org).…”