ABSTRACT
Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at dentate gyrus-CA3 excitatory synapses culminate in impaired coding of new spatial information in CA3 and CA1 and disrupted behavior in vivo. These results highlight the vulnerability of dentate gyrus-CA3 networks to aberrant human chromosome 21 gene expression and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in Down syndrome.
Subject(s)
CA3 Region, Hippocampal/physiopathology , Chromosomes, Human, Pair 21 , Dentate Gyrus/physiopathology , Disease Models, Animal , Down Syndrome/physiopathology , Nerve Net/physiopathology , Animals , CA3 Region, Hippocampal/pathology , Chromosomes, Human, Pair 21/genetics , Dentate Gyrus/pathology , Down Syndrome/genetics , Down Syndrome/pathology , Humans , Male , Maze Learning/physiology , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Nerve Net/pathology , Organ Culture Techniques , Trisomy/geneticsABSTRACT
Several studies have shown that the piriform cortex is involved in learning processes and pyramidal cell activity does not only encode the odour quality but is also related to contextual information about past experience and future action. To study how odour-specific patterns in neuronal activity are established we used an odour discrimination go/no go task with water reinforcement for analysing extracellular single cell activity in anterior piriform cortex in freely moving rats. During conditioning single cells responded to different task events. Of the cells 52% participate in odour sampling and 87% were involved in odour discrimination. More than half of the responses to odours were inhibitory responses. Seventeen percent changed their activity for nose-poke only. The activity of 33% was related to reinforcement. Once established the pattern of reaction to the odour was preserved for several days. It is suggested that the anterior part of the piriform cortex is not involved in odour coding only. However, learning-related plasticity was not observed in this area.
