Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum

Abstract

Dopamine is a critical modulator of striatal function; its absence produces Parkinson's disease. Most cellular actions of dopamine are still unknown. This work describes the presynaptic actions of dopaminergic receptor agonists on GABAergic transmission between neostriatal projection neurons. Axon collaterals interconnect projection neurons, the main axons of which project to other basal ganglia nuclei. Most if not all of these projecting axons pass through the globus pallidus. Thus, we lesioned the intrinsic neurons of the globus pallidus and stimulated neostriatal efferent axons antidromically with a bipolar electrode located in this nucleus. This maneuver revealed a bicuculline-sensitive synaptic current while recording in spiny cells. D 1 receptor agonists facilitated whereas D 2 receptor agonists depressed this synaptic current. In contrast, a bicuculline-sensitive synaptic current evoked by field stimulation inside the neostriatum was not consistently modulated, in agreement with previous studies. The data are discussed in light of the most recent experimental and modeling results. The conclusion was that inhibition of spiny cells by axon collaterals of other spiny cells is quantitatively important; however, to be functionally important, this inhibition might be conditioned to the synchronized firing of spiny neurons. Finally, dopamine exerts a potentially important role regulating the extent of lateral inhibition.

Voluntary Exercise and Sucrose Consumption Enhance Cannabinoid CB1 Receptor Sensitivity in the Striatum

“…Accordingly, striatal GABAergic principal neurons, besides inhibiting basal ganglia output nuclei, form functional synapses through their recurrent axon collaterals, establishing a feedback control over striatal neuron activity (Tunstall et al, 2002;Guzman et al, 2003;Koos et al, 2004;Gustafson et al, 2006). Inputs from GABAergic interneurons are another important source of synaptic inhibition of projection neurons, giving rise to a feed-forward inhibitory pathway that is independent of striatal output (Plenz 2003;Tepper et al, 2004;Gustafson et al, 2006).…”

Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses

“…Numerous functions of the NSt are thought to depend on this inhibition (12,(19)(20)(21)(22), such as the selection and organization of learned motor synergies and contrast enhancement (20)(21)(22)(23)(24)(25). Another form of neostriatal inhibition is due to local circuit fast-spiking (FS) interneurons (13,14,(26)(27)(28)(29)(30)(31)(32). The inhibition from FS interneurons is stronger than that between SPNs (13,14,(26)(27)(28)(29)(30)(31)(32).…”

“…Another form of neostriatal inhibition is due to local circuit fast-spiking (FS) interneurons (13,14,(26)(27)(28)(29)(30)(31)(32). The inhibition from FS interneurons is stronger than that between SPNs (13,14,(26)(27)(28)(29)(30)(31)(32). But inhibition between SPNs makes the majority of contacts (12,28,32).…”

“…The inhibition from FS interneurons is stronger than that between SPNs (13,14,(26)(27)(28)(29)(30)(31)(32). But inhibition between SPNs makes the majority of contacts (12,28,32). Both types of inhibition exhibit STD (13,14).…”

“…In its absence, the circuit functionally collapses, inducing the devastating signs of ParkinsonЈs disease (34)(35)(36). Although pre-and postsynaptic actions of dopamine have been described (24,32,37,38), a global action with a potential impact at the circuit level is not known. Here we show that STD between SPNs can be regulated by the dopaminergic system (6,32,39).…”