Optogenetic Stimulation of the Anterior Thalamic Nuclei Ameliorates Impaired Spatial Memory in Rats With Mammillothalamic Tract Lesions

Barnett, S.C. , McNaughton, N., Perry, B.A.L., Young, C.K., Hughes, S.M., Parr-Brownlie, L.C. and Dalrymple-Alford, J.C. (2020) Optogenetic Stimulation of the Anterior Thalamic Nuclei Ameliorates Impaired Spatial Memory in Rats With Mammillothalamic Tract Lesions. 12th FENS Forum of Neuroscience, 11-15 Jul 2020.

Abstract

Aims: Damage to the mammillothalamic tract (MTT) produces clinical amnesia and memory deficits in animal lesion models. These deficits reflect the loss of fibres terminating in the anterior thalamic nuclei (ATN) and thus impact the function of the extended memory system. We examined whether optogenetic stimulation of the glutamatergic ATN efferents would improve the behavioural and neural changes produced by MTT lesions. Methods: Rats with bilateral MTT lesions received viral vector (LV-CaMKIIa-ChR2 (H134R)-mCherry) infusions in the ATN. Spatial memory was tested using a 12-arm radial arm maze (RAM). The effects of no stimulation, optogenetic stimulation with blue light (465 nm; to activate channelrhodopsin) or orange light (620 nm; control condition) on memory performance were assessed using a counterbalanced design. Rats received regular or closed-loop theta burst stimulation (TBS) in the ATN at a frequency of 8.5 Hz. Results: Regular TBS with blue light produced a marked improvement in spatial memory performance in the MTT lesion group. No effects were found in any other stimulation conditions. TBS with blue light substantially increased neuronal activation in hippocampal CA1 and granular retrosplenial cortex, measured by zif268 immunohistochemistry. It also increased power spectral density in the ATN, hippocampus, and prefrontal cortex, plus ATN-hippocampal and ATN-prefrontal spectral coherence was also increased. Conclusions: Spatial memory deficits after MTT lesions can be ameliorated through selective optogenetic stimulation of the ATN. This recovery was associated with widespread neuronal changes in the extended hippocampus system that is important for memory function.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Barnett, Dr Sophie
• Authors: Barnett, S.C., McNaughton, N., Perry, B.A.L., Young, C.K., Hughes, S.M., Parr-Brownlie, L.C., and Dalrymple-Alford, J.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience

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