Dopamine D₁/D₅Receptors Gate the Acquisition of Novel Information through Hippocampal Long-Term Potentiation and Long-Term Depression

Abstract

Hebbian learning models require that neurons are able to both strengthen and weaken their synaptic connections. Hippocampal synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), has been implicated in both spatial memory formation as well as novelty acquisition. In addition, the ventral tegmental area-hippocampal loop has been proposed to control the entry of information into long-term memory, whereas the dopaminergic system is believed to play an important role in information acquisition and synaptic plasticity. D 1 /D 5 dopamine receptors are positively coupled to adenylyl cyclase and have been to modulate certain forms of synaptic plasticity, particularly in vitro. We investigated how D 1 /D 5 dopamine receptors modify long-lasting synaptic plasticity at CA1 synapses of adult freely moving rats and found that receptor activation lowered the threshold for the induction of both LTP and LTD. Specific types of learning are associated with specific types of hippocampal synaptic plasticity. We found that objectconfiguration learning, facilitation of late-phase LTD by object exploration, and late-phase LTP by exploration of empty space were all prevented by D 1 /D 5 receptor antagonism. Furthermore, receptor antagonism prevented electrically induced late-LTP, whereas receptor activation facilitated induction of both LTP and LTD by patterned electrical stimulation. These findings suggest that the dopaminergic system, acting via D 1 /D 5 receptors, gates long-term changes in synaptic strength and that these changes are a critical factor in the acquisition of novel information.

Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration

“…Lisman and Grace (34) proposed that the detection of new information by the hippocampus is relayed to the ventral tegmental area (VTA) through the subiculum, accumbens, and ventral pallidum and that the VTA, in turn, projects to the hippocampus through dopaminergic fibers acting on D 1 receptors, where it enhances long-term potentiation (LTP) and learning. The hippocampal-VTA loop has, in fact, been found to be important for novelty detection (32), for the generation and maintenance of hippocampal LTP (35), and for memory consolidation (34,36). The VTA plays a key role in psychomotor stimulation, particularly in the generation of drug addiction, mediated by local glutamate receptors and dopamine projections to the accumbens and elsewhere (37)(38)(39)(40).…”

Dopaminergic signaling in dendritic spines

“…In hippocampal slices, blockade of D1-class receptors attenuated, and activation of them enhanced the early (< 60 min) [60] and the late (> 2 hr), protein synthesis-dependent maintenance phases of LTP in CA1 synapses in a cAMP-dependent manner [61]. In addition, activation of D1-class receptors lowered the threshold for both LTP and LTD at CA1 synapses in vivo [62]. Similarly, in deep layer PFC synapses and hippocampal-PFC synapses, agonists of D1-class receptors facilitated, whereas antagonists impaired, NMDAR-dependent LTP via cAMP-dependent mechanisms [63][64].…”

The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies

“…Central dopamine (DA) plays an important role in most, if not all, of the key cognitive and behavioral processes associated with pair bonding including olfaction, sexual behavior, learning, memory, and conditioning (Mitchell et al, 1992;Cheng et al, 2003;Hull et al, 2004;Hull et al, 2006;Lemon et al, 2006;Tillerson et al, 2006;El-Ghundi et al, 2007). DA, particularly in mesolimbic brain regions, has also been implicated in the mediation of a variety of natural rewards (Wise et al, 1989;Bozarth, 1991) including mating (Everitt, 1990) which facilitates pair bonding (Carter et al, 1990;Williams et al, 1992b;Insel et al, 1995b;Curtis et al, 2003a;Wang et al, 2004).…”