Dopamine-dependent synaptic plasticity in striatum during in vivo development

Abstract

The neurotransmitters dopamine (DA) and glutamate in the striatum play key roles in movement and cognition, and they are implicated in disorders of the basal ganglia such as Parkinson's disease. Excitatory synapses in striatum undergo a form of developmental plasticity characterized by a decrease in glutamate release probability. Here we demonstrate that this form of synaptic plasticity is DA and DA D2 receptor dependent. Analysis of spontaneous synaptic responses indicates that a presynaptic mechanism involving inhibition of neurotransmitter release underlies the developmental plasticity. We suggest that a major role of DA in the striatum is to initiate mechanisms that regulate the efficacy of excitatory striatal synapses, producing a decrease in glutamate release. The striatum is the point of entry of information into the basal ganglia, and it has important roles in motor control and habit learning (1, 2). The neocortex (3, 4) and thalamus (5) provide the major excitatory inputs to striatal medium spiny projection neurons (MSNs). Morphological studies have demonstrated that the majority of these afferent terminals impinge on the head of the spines on the dendrites of striatal MSNs (6, 7), whereas most dopaminergic afferent fibers coming from the substantia nigra make synapses on the necks of the same dendritic spines (8). This close anatomical localization of these two types of synapses suggests that dopamine (DA) released from the nigrostriatal afferent terminals may have modulatory effects on the excitatory signals generated from the cortex and thalamus (9).The importance of DA in normal striatal function is evidenced by the severe disruption of behavior observed in Parkinson's disease and after chemical lesions of nigral dopaminergic inputs to striatum (10). In fact, DA plays a variety of important physiological roles in striatum (11-15). However, the cellular physiological actions of DA that contribute to striatal function in vivo are not fully understood. In the present study, we wanted to examine the role of the DA system in plasticity of synaptic efficacy at striatal glutamatergic synapses during early postnatal development.Long-term changes in synaptic efficacy have been postulated to be cellular mechanisms underlying learning and memory (16). Synaptic plasticity of this type may also be involved in maturation of central synapses. One form of synaptic plasticity that may play an important role in maturation of excitatory synapses in the striatum is a decrease in the efficacy of transmission that takes place during weeks 2-3 of postnatal development (17,18). This decrease in efficacy appears to involve a decrease in glutamate release. However, little is known about the role of different striatal neurotransmitters in this developmental plasticity.To determine whether DA plays a role in the synaptic plasticity during maturation of excitatory striatal synapses we examined synaptic transmission at glutamatergic synapses in two animal models over the period from postnatal day (PD) 12 to PD29. One model was a...

Inversion of Dopamine Responses in Striatal Medium Spiny Neurons and Involuntary Movements

“…Such rate increases across all MSNs imply a generalized mechanism, which does not distinguish between direct and indirect pathways, possibly related to exaggerated glutamatergic inputs from the cortex after loss of presynaptic dopamine regulation (Galarraga et al, 1987; Tang et al, 2001). Increased glutamatergic signaling in projection neurons in conditions of definite parkinsonism is also indicated by (1) changes at the synaptic level, such as loss of spines and contacts that may be related to hyperactivity of cortical afferents (Anglade et al, 1996; Ingham et al, 1998) or increase of postsynaptic excitability to glutamatergic inputs (Day et al, 2006; Shen et al, 2007), and (2) alterations of NMDA receptors with regard to subunit composition, cellular distribution, and phosphorylation status (Chase et al, 1998; Dunah et al, 2000).…”

The ins and outs of the striatum: Role in drug addiction

“…drug-taking) lead to dopamine release in the striatum, which promotes long-term potentiation (LTP) in cortical synapses onto dMSNs while simultaneously producing long-term depression (LTD) in iMSNs. Conversely, during non-rewarding events, dopamine neurons pause, resulting in decreased dopamine release in the striatum, which increases the strength of cortical synapses onto iMSNs and reduces the strength of cortical synapses onto dMSNs (Reynolds et al, 2001, Tang et al, 2001, Calabresi et al, 2007, Kreitzer and Malenka, 2007, Cohen and Frank, 2009, Gerfen and Surmeier, 2011, Hong and Hikosaka, 2011). …”

Dysfunctional play and dopamine physiology in the Fischer 344 rat

“…Dopamine has been shown to play a key role in modulating the strength of cortical synapses, both acutely during simultaneous activity and chronically through processes such as long-term depression (LTD) and long-term potentiation (LTP) [57–61]. The majority of the research examining dopamine release and its modulation of cortical synapses in the rat has been performed in Sprague-Dawley rats, the outbred strain from which Fischer rats were derived [58, 59, 62–65].…”