The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat

Long-term morphological synaptic changes associated with homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats were analyzed using three-dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections from the molecular layer of the dentate gyrus. For the first time in morphological studies, the specificity of the effects of LTP and LTD on both spine and synapse ultrastructure was determined using an N-methyl-d-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid). There were no differences in synaptic density 24 h after LTP or LTD induction, and CPP alone had no effect on synaptic density. LTP increased significantly the proportion of mushroom spines, whereas LTD increased the proportion of thin spines, and both LTP and LTD decreased stubby spine number. Both LTP and LTD increased significantly spine head evaginations (spinules) into synaptic boutons and CPP blocked these changes. Synaptic boutons were smaller after LTD, indicating a pre-synaptic effect. Interestingly, CPP alone decreased bouton and mushroom spine volumes, as well as post-synaptic density (PSD) volume of mushroom spines.These data show similarities, but also some clear differences, between the effects of LTP and LTD on spine and synaptic morphology. Although CPP blocks both LTP and LTD, and impairs most morphological changes in spines and synapses, CPP alone was shown to exert effects on aspects of spine and synaptic structure

Anatomical model of information integration in prelimbic cortex in the rat [poster presentation]

Anatomical Model of Information Integration in Rat Prelimbic Cortex (Area 32) - : Poster 68.01. Prelimbic (PL) cortex (area 32) integrates strategic autonomic, limbic and cognitive information underlying spatiotemporal behaviour. A quantitative neuroanatomical model has been constructed to define the structural integration of identified afferent synaptic inputs within rat PL cortex. Using quantitative data defining the component neuronal densities and dendritic architectures of excitatory pyramidal cells and inhibitory interneurons, a dendrite model of rat PL cortex has been developed. In combination with anatomical anterograde tract-tracing data (defining the laminar distribution of identified afferent synaptic input from the basolateral amygdala, ventral CA1 hippocampus, lat. hypothalamus, mediodorsal thalamus and anterior insular cortex) the number of individual synaptic contacts between a given source of afferent input and the dendrites of specific classes of pyramidal and interneurons in PL cortex have been determined given a theoretically uniform pattern of target innervation. The results indicate very sparse connectivity (less than 5 synapses) between identified afferent axonal arbors and the dendrites of an individual target PL pyramid or interneuron. The theoretical data provide important insights into the parallel processing of uniformly distributed afferent information and local excitatory and inhibitory circuits within rat PL cortex. Sponsored by The Wellcome Trust and The Open University