Background Low-frequency (delta/theta) oscillations in the thalamocortical system are elevated in schizophrenia during wakefulness and are also induced in the NMDAR hypofunction rat model. To determine whether abnormal delta oscillations might produce functional deficits, we used optogenetic methods in awake rats. We illuminated channelrhodopsin-2 in the thalamic nucleus reuniens (RE) at delta frequency and measured the effect on working memory performance (the RE is involved in working memory (WM), a process affected in schizophrenia (SZ)). Methods We injected RE with a virus (AAV) to transduce cells with channelrhodopsin-2. An optical fiber was implanted just dorsal to the hippocampus in order to illuminate RE axon terminals. Results During optogenetic delta frequency stimulation, rats displayed a strong WM deficit. On the following day, performance was normal if illumination was omitted. Conclusions The optogenetic experiments showed that delta frequency stimulation of a thalamic nucleus is sufficient to produce deficits in WM. This result supports the hypothesis that delta frequency bursting in particular thalamic nuclei has a causal role producing WM deficits in this SZ. The action potentials in these bursts may jam communication through the thalamus, thereby interfering with behaviors dependent on WM. Studies in thalamic slices using the NMDAR hypofunction model show that delta frequency bursting is dependent on T-type Ca2+ channels, a result that we confirmed here in vivo. These channels, which are strongly implicated in SZ by GWAS studies, may thus be a therapeutic target for treatment of SZ.
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