AbstractDown Syndrome (DS) in humans is caused by trisomy of chromosome 21 and is marked by prominent difficulties in learning and memory. Decades of research have demonstrated that the hippocampus is a key structure in learning and memory, and recent work with mouse models of DS have shown changes in spectral coherence in the field potentials of hippocampus and regions important for executive function such as prefrontal cortex. One of the primary functional differences in DS is thought to be an excess of GABAergic innervation from Medial Septum (MS) to regions such as hippocampus. In these experiments, we probe in detail the activity of region CA1 of the hippocampus using in vivo electrophysiology in the Ts65Dn mouse model of DS in comparison to their non-trisomic 2N littermates. We find changes in hippocampal phenomenology that suggest that MS output, which drives theta rhythm in the hippocampus, is strongly altered. Moreover, we find that this change affects the phasic relationship of both CA1 place cells and gamma rhythms to theta. Since the phasic relationship of both of these aspects of hippocampal phenomenology to theta are thought to be critical for the segregation of encoding and retrieval epochs within hippocampus, it is likely that these changes are the neural substrates of the learning and memory deficits seen both in human DS and animal models such as Ts65Dn.
Disordered phasic relationships between hippocampal place cells, theta, and gamma rhythms in the Ts65Dn mouse model of Down Syndrome
