Delta frequency optogenetic stimulation of the thalamic nucleus reuniens is sufficient to produce working memory deficits: relevance to schizophrenia.

摘要: Abstract Background Low-frequency (delta/theta) oscillations in the thalamocortical system are elevated schizophrenia during wakefulness and also induced N -methyl-D-asparate receptor hypofunction rat model. To determine whether abnormal delta might produce functional deficits, we used optogenetic methods awake rats. We illuminated channelrhodopsin-2 thalamic nucleus reuniens (RE) at frequency measured effect on working memory (WM) performance (the RE is involved WM, a process affected [SZ]). Methods injected with adeno-associated virus to transduce cells channelrhodopsin-2. An optical fiber was implanted just dorsal hippocampus order illuminate axon terminals. Results During stimulation, rats displayed strong WM deficit. On following day, normal if illumination omitted. Conclusions The experiments show that stimulation of sufficient deficits WM. This result supports hypothesis bursting particular nuclei has causal role producing SZ. action potentials these bursts may "jam" communication through thalamus, thereby interfering behaviors dependent Studies slices using model T-type Ca 2+ channels, confirmed here vivo. These which strongly implicated SZ by genome-wide association studies, thus be therapeutic target for treatment