Hippocampal and cortico-striatal contributions to spatial learning: early versus late Morris water maze learning

Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}The ability to learn new skills or habitsas a result of practice is one of the most distinguished features of biologicalsystems. Neuroplastic processes and changes in synaptic connections arephenomena at the systems and molecular neuroscience level enabling differentforms of learning and memory. In this dissertation we aimed to elucidate someof these neuroplastic mechanisms associated with early and late complex watermaze learning. The main goal was to visualize possible network activity betweendifferent brain regions for which independent involvement in water mazelearning was already established a priori.The major part of this study comprisedthe quantitative analysis of immediate early gene expression levels in thehippocampus (CA1 and CA3), striatum (DMS, sDMS and DLS) and prefrontal cortex(aCC, PL and IL) by means of in situhybridization experiments for the molecular activity marker zif268 and the molecular plasticitymarkers Homer1a and arc. Through these analyses we soughtto identify learning phase-related differences in the contributions of thesedistinct subregions of the brain. Furthermore, this IEG imaging approach alsoallowed us to characterize the nature of interactions between subregions in theintact mouse brain. With respect to the hippocampus, surface biotinylationassays in acute brain slices (ASBA) combined with Western analysis enabled usto measure modifications in the membrane expression of specific cell surfaceproteins.In the corticostriatal system, we have found synergisticactivity dynamics (zif268 expression)over the course of learning in the (superior) dorsomedial striatum, theprelimbic and the anterior cingulate cortex, with these regions being mostactive during goal-directed early learning. Also, parallel dynamics in activitywere found in the dorsolateral striatum and infralimbic cortex, with bothregions mediating habitual water maze performance. During early task
acquisition, these two corticostriatal circuits were shown to develop simultaneously.However, arc expression levelssuggested that the goal-directed corticostriatal loop controlled behavioraloutput during early spatial learning. Upon overtraining, we demonstrated ashift in behavioral control to the habitual corticostriatal circuit. Withrespect to the hippocampal system, we demonstrated a continuous activation (zif268 expression) during water mazeperformance in CA1, not CA3. However, task-specific engagement in CA1 was only foundduring the goal-directed early learning phase. Since ASBA analysis onlydetected modifications of the NMDAR subunit composition during early learning,we suggest that the hippocampus indeed mediates goal-directed early learning incorrespondence with the corticostriatal circuit comprising the (superior)dorsomedial striatum, the prelimbic and the anterior cingulate cortex.

Jaar van publicatie:2012

Toegankelijkheid:Open