Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity

Abstract

Dopamine (DA) is important to a wide range of striatal functions, including associative learning and habit formation. At synapses between cortical pyramidal neurons and principal striatal medium spiny neurons (MSNs), postsynaptic D1 and D2 DA receptors are postulated to be necessary for the induction of long-term potentiation and depression, respectively. Because these receptors are restricted to two distinct MSN populations, this postulate demands that synaptic plasticity be unidirectional in each cell type. Using brain slices from DA receptor transgenic mice, we show that this is not the case. Rather, DA plays complementary roles in these two types of MSN to ensure that synaptic plasticity is bidirectional and Hebbian. In models of Parkinson's disease, this system is thrown out of balance, leading to unidirectional changes in plasticity that could underlie network pathology and symptoms.

Computational models of reinforcement learning: the role of dopamine as a reward signal

“…The resulting transient activity increase in those NoGo cells that are concurrently excited by corticostriatal glutamatergic input is associated with activity-dependent synaptic strengthening (LTP), such that the system is more likely to suppress the maladaptive action in future encounters with the same sensory event. This effect is also consistent with studies in which a lack of D2 receptor stimulation (a ''pause'' in DA release) was associated with LTP in striatopallidal cells (Shen et al 2008). The model has been used to simulate the effects of Parkinson's disease and pharmacological manipulations on learning and decision making processes in humans, and predicted that learning from positive and negative outcomes would be modulated in opposite directions by such treatments, as confirmed empirically (Frank et al 2004; for review see Cohen and Frank 2009).…”

“…DA bursts during positive prediction errors increase synaptic connection weights in subpopulations of Go-D1 cells that are concurrently excited by corticostriatal glutamatergic input, while also decreasing weights in NoGo-D2 cells. This enables the network to be more likely to repeat actions that are associated with positive reward prediction errors (Frank 2005), and is consistent with recent studies of synaptic plasticity showing D1-dependent LTP in striatonigral cells and D2-dependent LTD in striatopallidal cells (Shen et al 2008). Moreover, in the model, DA pauses during negative prediction errors releasing NoGo cells from the tonic inhibition of DA onto highaffinity D2 receptors.…”

“…The influence of dopamine on synaptic plasticity depends on numerous factors including the targeted cell type, the specific receptors activated and the brain region under consideration (Bissière et al 2003;Calabresi et al 2007;Otani et al 2003;Shen et al 2008;Wickens 2009;Yao et al 2008). Reinforcement learning results from the dynamical interaction between numerous brain networks mediating the acquisition of conditioning tasks and action selection.…”

“…Of course, several biophysical details are omitted in these models of corticostriatal circuitry. For example, future modeling work should incorporate STDP within the context of the basal ganglia circuitry to examine the role of spike-timing, together with the roles of other neurochemicals, such as adenosine, on corticostriatal plasticity (Shen et al 2008).…”

Approche optogénétique de suppression de la plasticité synaptique induite par la cocaïne

“…La stimulation de ces neurones à une basse fréquence (1 Hz, protocole de long term depression [LTD]) permet la « dépotentiali-sation » de la transmission glutamatergique sur les MSN par un mécanisme postsynaptique (réduction du nombre de AMPAR à la membrane des MSN). L'application de ce traitement abolit complètement la sensibilisation locodes MSN dépend de la stimulation de ces mêmes récepteurs [10]. La LTP est une forme de plasticité synaptique dans laquelle l'activité renforce les synapses glutamatergiques, généralement via l'insertion dans la membrane plasmique du neurone postsynaptique d'un plus grand nombre de récepteurs au glutamate (de type -amino-3-hydroxy-…”