Electrical and pharmacological manipulations of the nucleus accumbens core impair synaptic plasticity in the dentate gyrus of the rat.

The interest on the physiology of the nucleus accumbens (NAcc) has grown in recent years given its relationship to addictive behaviours, and the possibility to treat them by interacting with NAcc function. We have shown that the prior stimulation of the core region blocks induction of long-term potentiation (LTP) at the dentate gyrus in anaesthetized rats, while the shell facilitated it. In the present study we have confirmed and expanded those results testing the effects of core and shell stimulation in freely moving rats, as well as the effect of blocking D1 receptors in the NAcc. Our results show that shell stimulation had no effect on baseline recordings of the field excitatory postsynaptic potential (fEPSP) or the population spike amplitude (PSA) for 24 h. Core stimulation did not modify baseline-fEPSP, but significantly depressed PSA up to 8 h. LTP maintenance was not modified; neither by core nor shell stimulation after its induction, but LTP induction was impaired (both in the fEPSP and PSA) by core stimulation 15 min before induction. Shell stimulation showed a slight facilitating effect. Previous, topical application of a dopaminergic-receptor antagonist (SCH23390) into the NAcc produced a significantly depressed baseline fEPSP and PSA, as well as LTP measured in both components of the evoked potentials. Our results confirm a dual role of stimulation of NAcc sub-regions on hippocampal baseline synaptic transmission, and LTP induction when activated before induction. In contrast, stimulation of the NAcc had no influence on an already ongoing dentate gyrus LTP. A role for dopaminergic innervation to the NAcc, modifying susceptibility for synaptic plasticity outside the NAcc is also suggested by our results.

Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats.

Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by subcortical, heterosynaptic afferents.

Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocampal slices during long-term potentiation in vitro.

Molecular events associated with mnemonic processes and neuronal plasticity are postulated to result in functional changes in synaptic structure. One possible site is the post-synaptic density, where activity-dependent changes modulate signal transduction cascades. In this report, we detail spatial-temporal changes for phosphodiesterase 4B (PDE4B) proteins and their substrate cAMP within three neuronal fractions during early and late long-term potentiation (LTP). The cAMP-dependent protein kinase A cascade--which can be regulated by distinct PDE4B activity--is required for mnemonic processes as well as mechanisms of neuronal plasticity, such as those during the maintenance or late-LTP. Fluorescence in situ hybridization studies (FISH) identified no translocation of PDE4B3 from the soma after late-LTP induction indicating a subtle, local control of PDE4B activity. Protein changes were detected within the PSD-enriched fraction. From these results, we conclude that either the changes in PDE4B are due to modulation of pre-existing mRNA, or that the protein is specifically translocated to activated synaptic structures. Furthermore, we report late changes in cAMP levels in the somato-dendritic fraction and discuss this result with the increased PDE4B1/3 doublet in the PSD-enriched fraction.

Regulation of the phosphodiesterase PDE4B3-isotype during long-term potentiation in the area dentata in vivo.

Hippocampal long-term potentiation (LTP) is the most prominent cellular model underlying learning and memory formation. However, which cellular processes are involved in maintaining LTP remains largely unknown. We have previously detailed temporal modulations of cyclic adenosine monophosphate (cAMP) and a cAMP-specific phosphodiesterase, PDE4B3, after LTP-induction and its maintenance in hippocampal area CA1 in vitro. To test whether other hippocampal sub-structures are characterised by similar mechanisms, tissue from the area dentata of freely moving rats was analysed at different LTP-time points. The tissue was fractionated into three components, where PDE4B-levels and cAMP-concentrations were measured. In contrast with data obtained in area CA1, we now detail an LTP-specific translational, but not transcriptional regulation of PDE4B3 within the first 8 h after tetanization and present spatio-temporal changes of PDE4B proteins and cAMP that is LTP-specific.