Ventral striatal plasticity and spatial memory

Abstract

Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein-induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs longterm spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation. T he formation of long-term memories is believed to involve a dynamic process by which a labile memory is progressively converted into a more stable and potentially permanent trace. Evidence for such a time-dependent process comes from studies demonstrating that electroconvulsive shock produces amnesia only if delivered shortly after learning, whereas the same treatment is ineffective when delivered several hours later (1). Long-term memory is accompanied by changes in neuronal morphology and connectivity, and these alterations are thought to be essential for the stabile encoding of new information (2). This transformation has been suggested to depend upon plastic changes that involve a sequence of specific and coordinated cellular processes. These begin with neurotransmitter receptor activation that induces shortterm changes in synaptic efficacy based on receptor phosphorylation and trafficking (3, 4). Subsequently, alterations in gene expression and protein synthesis occur that are the basis for longterm structural modifications (5, 6).A key issue in the study of memory in vertebrates is the brain site at which these processes occur. Clinical evidence in humans suggests that structures within the medial temporal lobe (MTL) play a prominent role in long-term memories. MTL lesions induce profound deficits in the formation of long-lasting declarative memories while sparing the acquisition of nondeclarative memories such as visual-motor skills (7,8). Such findings suggest that the hippocampus might be an essential site where plasticity occurs in the initial steps of declarative memory stabilization. Accordingly, those molecular events thought to be crucial for the long-term encoding of memories such as regulation of gene expression and protein synthesis, as well as structural changes, have been described in the hippocampus after spatial learning (6, 9, 10).Recent experimental evidence, however, demonstrates that structures different from the hippocampus might also be involved in ...

Spatial memory, plasticity and nucleus accumbens

“…Exposure to a novel environment is associated with an increase in CREB phosphorylation (Alvarez-Jaimes et al, 2005a) and Fos levels in the NAc . Intra-NAc administrations of AS-ODN targeted against CREB impaired long-but not short-term spatial memory in the object displacement task ( Figure 1 ) (Ferretti et al, 2010). A similar impairment of LTM in the object displacement task and in the MWM has been observed after post-training intra-NAc injection of the protein synthesis inhibitor anisomycin (Ferretti et al, 2010).…”

Adaptation, Expertise, and Giftedness: Towards an Understanding of Cortical, Subcortical, and Cerebellar Network Contributions

“…Ferretti, Roullet, and Sargolini have demon-strated that the ventral striatum plays a critical role in interacting with the medial temporal lobe during spatial information processing and spatial memory. This demonstrates that cortical-basal ganglia interactions govern "ruleguided" behaviors, including those associated with making and storing visual graphic representations [310]. While mathematical calculation models differ considerably in their assumptions concerning the representation of arithmetic facts, one model proposes that these mathematical facts are stored as sequences, which would again be the product of cortical-striatal interactions [311].…”

Is memory consolidation a multiple-circuit system?

“…Accordingly, protein synthesis blockers applied in either the amygdala or the insular cortex affect taste memory consolidation. Although it remains to be demonstrated whether similar interaction could be occurring among the hippocampus, ventral striatum, and cortical areas during spatial memory consolidation; the results of Ferretti et al (8) suggest that different brain areas outside the medial temporal lobe could be participating in the consolidation of declarative memories. …”

“…In other words, the axonal rearrangement was seen only when animals consolidated explicit but not implicit spatial memory components. Interestingly, Ferretti et al (8) further demonstrate that the ventral striatum is involved by means of a protein synthesis blocker and transcriptional factor antisense in the spatial memory explicit but not implicit response of memory consolidation. Therefore, these findings show that some areas that are not considered to be part of the medial temporal lobe could also be significantly involved in spatial memory consolidation.…”

“…In several papers it has been demonstrated that other structures in addition to the hippocampus, such as the nucleus accumbens or some cortical regions, are involved in episodic or recognition memory consolidation (6,7). In PNAS, Ferretti et al (8) show that the ventral striatum also has an important role in declarative memory consolidation. In their paper, they were able to show in two differentially motivated spatial memory tasks (object in context and water maze task) that reduction of a transcriptional factor such as CREB (cAMP-response element binding protein) and protein synthesis inhibition impaired spatial memory consolidation for both tasks.…”