Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum

doi:10.1016/j.neuropharm.2010.01.008

Neuropharmacology

Volume 58, Issue 7, June 2010, Pages 951-961

https://doi.org/10.1016/j.neuropharm.2010.01.008 Get rights and content

Abstract

The dorsal striatum is a large forebrain region involved in action initiation, timing, control, learning and memory. Learning and remembering skilled movement sequences requires the dorsal striatum, and striatal subregions participate in both goal-directed (action-outcome) and habitual (stimulus–response) learning. Modulation of synaptic transmission plays a large part in controlling input to as well as the output from striatal medium spiny projection neurons (MSNs). Synapses in this brain region are subject to short-term modulation, including allosteric alterations in ion channel function and prominent presynaptic inhibition. Two forms of long-term synaptic plasticity have also been observed in striatum, long-term potentiation (LTP) and long-term depression (LTD). LTP at glutamatergic synapses onto MSNs involves activation of NMDA-type glutamate receptors and D1 dopamine or A2A adenosine receptors. Expression of LTP appears to involve postsynaptic mechanisms. LTD at glutamatergic synapses involves retrograde endocannabinoid signaling stimulated by activation of metabotropic glutamate receptors (mGluRs) and D2 dopamine receptors. While postsynaptic mechanisms participate in LTD induction, maintained expression involves presynaptic mechanisms. A similar form of LTD has also been observed at GABAergic synapses onto MSNs. Studies have just begun to examine the roles of synaptic plasticity in striatal-based learning. Findings to date indicate that molecules implicated in induction of plasticity participate in these forms of learning. Neurotransmitter receptors involved in LTP induction are necessary for proper skill and goal-directed instrumental learning. Interestingly, receptors involved in LTP and LTD at glutamatergic synapses onto MSNs of the “indirect pathway” appear to have important roles in habit learning. More work is needed to reveal if and when synaptic plasticity occurs during learning and if so what molecules and cellular processes, both short- and long-term, contribute to this plasticity.

Section snippets

Neurotransmitters in striatum: it's a jungle in there

The striatum is the major input nucleus of the basal ganglia, and as such it plays a crucial role in action control and action learning (Saint-Cyr et al., 1995, Graybiel, 1998, Lalonde and Botez-Marquard, 1997, Yin and Knowlton, 2006). These roles are accomplished via striatal generation of neuronal activity that initiates and terminates action sequences, processing of afferent inputs that influence this activity, and controlling the activity of downstream efferent target nuclei through

Short-term modulation of striatal synaptic transmission

Neuromodulation strongly impacts striatal function, and deficits in this more subtle type of synaptic communication play key roles in neurological disorders involving this brain region. A strong dopaminergic afferent input from the substantia nigra pars compacta innervates MSNs and striatal interneurons. The midbrain neurons that give rise to this input degenerate in Parkinson's disease, and it is clear that loss of dopaminergic input causes hypokinesia and other facets of this disorder.

Striatal LTP

Studies from a number of laboratories over the last 15–20 years have revealed two predominant forms of long-lasting synaptic plasticity at glutamatergic striatal synapses: long-term potentiation (LTP) and long-term depression (LTD) (see Kreitzer and Malenka, 2008, Wickens, 2009 for review) (Fig. 1). Striatal LTP is a long-lasting increase in the efficacy of glutamatergic synapses that is observed mainly at corticostriatal synapses (Charpier and Deniau, 1997, Calabresi et al., 1992c). Ideas

Synaptic plasticity in striatal-based learning and memory

It has long been known that the striatum, including the dorsal striatum, plays critical roles in learning and memory. Early studies implicated the dorsal striatum in response-based learning and instrumental conditioning (Divac et al., 1967, Konorski, 1967). More recent studies using excitotoxic lesions, neurochemical approaches, and direct measurement of striatal neuronal activity in vivo have revealed roles for the dorsal striatum in skill learning, response-based learning, and instrumental

Summary

Modulation of synaptic transmission either over the short- or long-term is a prominent mechanism for controlling striatal output, as activity of the MSN projection neurons is strongly influenced by their synaptic inputs. Electrophysiological studies have now established two prominent forms of long-lasting synaptic plasticity in striatum, LTP and LTD, as well as several forms of short-lasting synaptic modulation. The molecular mechanisms of these forms of plasticity are still being determined.

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Mini-reviewNeurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum

Abstract

Section snippets

Neurotransmitters in striatum: it's a jungle in there

Short-term modulation of striatal synaptic transmission

Striatal LTP

Synaptic plasticity in striatal-based learning and memory

Summary

Neurosci. Lett.

Brain Res. Mol. Brain Res.

Neuron

Neurosci. Lett.

Neuropharmacology

Prog. Neurobiol.

Neurobiol. Learn. Mem.

Biol. Psychiatry

Curr. Biol.

Behav. Brain Res.

Trends Neurosci.

Brain Res.

Prog. Neurobiol.

Neurobiol. Learn. Mem.

Neuropharmacology

Neuroscience

Neurosci. Lett.

Neuron

Neurosci. Lett.

Neurosci. Lett.

Neuroscience

Neurobiol. Learn. Mem.

Neurobiol. Dis.

Neuropharmacology

Combined activation of L-type Ca2+ channels and synaptic transmission is sufficient to induced striatal long-term depression

J. Neurosci.

Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step

Proc. Natl. Acad. Sci. U.S.A.

Frequency-dependent inversion of net striatal output by endocannabinoid-dependent plasticity at different synaptic inputs

J. Neurosci.

Endocannabinoid-dependent plasticity at GABAergic and glutamatergic synapses in the striatum is regulated by synaptic activity

Eur. J. Neurosci.

Responses of tonically active neurons in the primate's striatum undergo systematic changes during behavioral sensorimotor conditioning

J. Neurosci.

Dopamine modulates release from corticostriatal terminals

J. Neurosci.

Spontaneous activity of neostriatal cholinergic interneurons in vitro

J. Neurosci.

Loss of muscarinic autoreceptor function impairs long-term depression but not long-term potentiation in the striatum

J. Neurosci.

Excitatory GABAergic effects in striatal projection neurons

J. Neurophysiol.

Involvement of GABA systems in feedback regulation of glutamate- and GABA-mediated synaptic potentials in rat neostriatum

J. Physiol.

Long-term synaptic depression in the striatum: physiological and pharmacological characterization

J. Neurosci.

Long-term potentiation in the striatum is unmasked by removing the voltage-dependent magnesium block of NMDA receptor channels

Eur. J. Neurosci.

Heterogeneity of metabotropic glutamate receptors in the striatum: electrophysiological evidence

Eur. J. Neurosci.

Post-receptor mechanisms underlying striatal long-term depression

J. Neurosci.

Blockade of M2-like muscarinic receptors enhances long-term potentiation at corticostriatal synapses

Eur. J. Neurosci.

Dopamine and cyclic adenosine 3′,5′ monophosphate-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity

J. Neurosci.

Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia

Brain

A critical interaction between dopamine D2 receptors and endocannabinoids mediates the effects of cocaine on striatal gabaergic transmission

Neuropsychopharmacology

Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated

Proc. Natl. Acad. Sci. U.S.A.

In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation

Proc. Natl. Acad. Sci. U.S.A.

Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses

Proc. Natl. Acad. Sci. U.S.A.

Decreased frequency but not amplitude of quantal synaptic responses associated with expression of corticostriatal long-term depression

J. Neurosci.

M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain

J. Neurosci.

The role of the nucleus accumbens in instrumental conditioning: evidence of a functional dissociation between accumbens core and shell

J. Neurosci.

Mini-review
Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum

Combined activation of L-type Ca²⁺ channels and synaptic transmission is sufficient to induced striatal long-term depression