Anterior thalamic nuclei neurons sustain memory

S C Barnett; L C Parr-Brownlie; B A L Perry; C K Young; H E Wicky; S M Hughes; N McNaughton; J C Dalrymple-Alford

doi:10.1016/j.crneur.2021.100022

Anterior thalamic nuclei neurons sustain memory

Curr Res Neurobiol. 2021 Sep 24:2:100022. doi: 10.1016/j.crneur.2021.100022. eCollection 2021.

Authors

S C Barnett^{1

2

3}, L C Parr-Brownlie^{2

4

5}, B A L Perry^{1

2

6}, C K Young^{5

7}, H E Wicky^{2

5

8}, S M Hughes^{2

5

8}, N McNaughton^{5

7}, J C Dalrymple-Alford^{1

2

9

10}

Affiliations

¹ School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand.
² Brain Research New Zealand, Co-hosted by the University of Auckland and University of Otago, New Zealand.
³ Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
⁴ Department of Anatomy, University of Otago, Dunedin, New Zealand.
⁵ Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
⁶ Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
⁷ Department of Psychology, University of Otago, Dunedin, New Zealand.
⁸ Department of Biochemistry, University of Otago, Dunedin, New Zealand.
⁹ New Zealand Brain Research Institute, Christchurch, New Zealand.
¹⁰ Department of Medicine, University of Otago, Christchurch, New Zealand.

Abstract

A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia. However, there is only limited and indirect support that the output of ATN neurons actively enhances memory. Here, in rats, we first showed that mammillothalamic tract (MTT) lesions caused a persistent impairment in spatial working memory. MTT lesions also reduced rhythmic electrical activity across the memory system. Next, we introduced 8.5 Hz optogenetic theta-burst stimulation of the ATN glutamatergic neurons. The exogenously-triggered, regular pattern of stimulation produced an acute and substantial improvement of spatial working memory in rats with MTT lesions and enhanced rhythmic electrical activity. Neither behaviour nor rhythmic activity was affected by endogenous stimulation derived from the dorsal hippocampus. Analysis of immediate early gene activity, after the rats foraged for food in an open field, showed that exogenously-triggered ATN stimulation also increased Zif268 expression across memory-related structures. These findings provide clear evidence that increased ATN neuronal activity supports memory. They suggest that ATN-focused gene therapy may be feasible to counter clinical amnesia associated with dysfunction in the mammillary body-ATN axis.

Keywords: Anterior thalamic nuclei; Episodic memory; Extended hippocampal system; Glutamatergic; Immediate early gene; Lesions; Mammillothalamc tract; Optogenetics; Recovery of function; Spatial memory; Theta; Working memory.