Excitatory synaptic transmission in neostriatal neurons: regulation by cyclic AMP-dependent mechanisms

Abstract

The purpose of the present study was to examine whether cAMP-dependent mechanisms regulated excitatory synaptic transmission in the neostriatum. A brain slice preparation was utilized for intracellular recordings of the excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation. Bath application of forskolin, an activator of adenylate cyclase, enhanced the EPSP amplitude and duration. This potentiation was dose dependent and did not occur with the inactive analog 1,9-dideoxyforskolin. Forskolin potentiation was unaltered by treatment with the GABAA receptor antagonist bicuculline. Furthermore, two inhibitors of cAMP-dependent protein kinase (PKA), Rp-cAMPS and IP20-amide, attenuated forskolin's enhancement of the EPSP. In addition, the PKA activator Sp-cAMPS enhanced excitatory synaptic transmission. Interestingly, treatment with PKA inhibitors alone depressed while the phosphatase inhibitor okadaic acid enhanced the synaptic response. These results suggest a role for tonic kinase and phosphatase activity in regulating excitatory synaptic transmission in the neostriatum. Finally, forskolin was found to enhance the responses of neostriatal neurons to glutamate receptor agonists. This potentiation, which occurred in the presence of tetrodotoxin, provides at leas part of the explanation for the cAMP/PKA-dependent regulation of the EPSP. Overall, these results suggest a role for the adenylate cyclase cascade in the regulation of excitatory synaptic transmission in the neostriatum.

PK 11195 blockade of benzodiazepine‐induced inhibition of forskolin‐stimulated adenylate cyclase activity in the striatum

“…Therefore, Gi-coupled BZ receptors in the brain may mediate suppression of the ubiquitous second messenger, cyclic AMP, contributing to the diverse psychotropic effects of the BZs, melatonin and related indoleamines. There is evidence that cyclic AMP/protein kinase A (PKA)-dependent mechanisms are involved in the regulation of excitatory synaptic transmission in the CNS (Colwell & Levine, 1995). In keeping with the above, the a2-adrenoceptor agonist, clonidine, which inhibits adenylate cyclase activity and cyclic AMP synthesis in the rat brain (Kitamura et al, 1985), is a potent anticonvulsant (Papanicolaou et al, 1982) and anxiolytic drug (Scheinin et al, 1989).…”

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

“…Indeed it is interesting to note that administrations of the D1 receptor antagonist induced similar behavioral patterns (ie a selective impairment in the reactivity to the spatial change) when injected into the PFC or the nucleus accumbens. There is now consistent experimental evidence suggesting that striatal glutamate receptor-channels undergo states of phosphorylation and dephosphorylation that can prolong or shorten the time of activation of the channels (Colwell and Levine, 1995;Umemiya and Raymond, 1997) and that these changes are under the control of D1 DA receptors (Chao et al, 2002). Such processes could explain the facilitatory effects of D1 receptors on the short-term processing of spatial information in the two structures.…”

D1Receptor Activation Enhances Evoked Discharge in Neostriatal Medium Spiny Neurons by Modulating an L-Type Ca2+Conductance

“…Here, D 1 agonists attenuate fast excitatory synaptic potentials attributable to activation of glutamatergic receptors of the AMPA /KA class and enhance the slower depolarizations attributable to NMDA receptors (Cepeda et al, 1993). These effects may be mediated in part by presynaptic mechanisms (Calabresi et al, 1987;Flores-Hernández et al, 1997), but they definitely have a postsynaptic component (Colwell and Levine, 1995). This postsynaptic component may involve voltage-dependent channels known to be targeted by the D 1 receptor pathway.…”