Ventro-Striatal plasticity in spatial learning and memory.
Well established is the importance of the hippocampus in spatial learning and memory, however, there is accumulating evidence suggesting the involvement of a more integrated circuit in spatial information processing and consolidation. The ventral striatum (VS) has been involved in both short and long-term spatial memory and receives dense glutamatergic projections from the ventral subiculum of the hippocampus (vSub). Therefore it has been suggested that hippocampal input might trigger the in the VS the molecular processes necessary for memory consolidation. Memory consolidation, requires at the beginning an increase in synaptic efficacy based on changes in synaptic receptors trafficking and conductance.Recent findings indicate that regulation of AMPA-R by phosphorylation at its GluR1 Ser845 and Ser831 sites is particularly relevant for the induction of different forms of synaptic plasticity in vivo, but their role in memory processes is still debated.
The purpose of the present study was In the first place to verify the functional relationship between hippocampus and VS in the processing of spatial information. Furthermore we wanted to investigate whether AMPA-R activation and phosphorylation, in this latter structure was needed for long-term spatial memory consolidation. To verify the first hypothesis we performed unilateral administrations of the AMPA antagonist into the vSub and into the contralateral VS, before training in the MWM task. The functional disconnection significantly impaired the ability to locate the correct quadrant on probe test 24 hours later. The findings confirm the role of VS and vSub in the processing of spatial information. Further they suggest that a serial transmission of information between the two brain regions is necessary in order to acquire the information necessary to locate the platform. To demonstrate that AMPA receptor phosphorylation was a necessary requirement for spatial memory stabilization we used an RNA aptamer that specifically binds and prevents AMPA receptor phosphorylation at Ser845 site in the VS. We found that this treatment was sufficient to induce a memory impairment on the probe trial.
These data, together with previous evidence in the literature, demonstrate the involvement of the hippocampal- VS pathway in the early stages of long-term stabilization of spatial information and that AMPA receptors phosphorylation within the VS is required for this process; further they strongly suggest that AMPA receptor phosphorylation could be triggered by the activation of the hippocampal-VS circuit.