Anterior thalamic nuclei neurons sustain memory

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.

Bifurcating Neurons In The Anterior Thalamic Nuclei

“…In support of this, electrophysiological recordings made in drug-resistant epilepsy patients suggest that the ATN integrate information from diverse cortical sources during encoding to guide successful recall (Sweeney-Reed et al, 2021). Other recent studies have shown that working memory in both humans and rats can be improved by stimulation of the ATN (Barnett et al, 2021; Liu et al, 2021). It would be especially informative to learn if the bifurcating ATN neurons have a pre-eminent role in enhancing memory.…”

“…Extensive clinical and experimental evidence supports the conclusion that the anterior thalamic nuclei (ATN) make a significant contribution to memory function (Aggleton, 2008; Aggleton et al, 2016; Barnett et al, 2021; Carlesimo et al, 2011; Dalrymple-Alford et al, 2015; Harding et al, 2000; Kim et al, 2009; Kopelman, 2015; Liu et al, 2021; Maillard et al, 2021; Sweeney-Reed et al, 2021; Wolff et al, 2015). This influence is consistent with the ATN’s strong reciprocal connections with three distinct memory structures, namely the medial prefrontal cortex (mPFC), retrosplenial cortex (RSC) and the hippocampal formation (HF) (Aggleton et al, 2016; Bubb et al, 2017; Mathiasen et al, 2017; Nelson, 2021; Shibata, 1993a, 1993b; van Groen et al, 1999; van Groen and Wyss, 1990; van Groen and Wyss, 1995).…”

Anterior thalamic nuclei: A critical substrate for non‐spatial paired‐associate memory in rats

“…As in previous studies (Aggleton & Nelson, 2015; Perry et al, 2018), the strongest effect was a marked reduction in IEG expression after ATN lesions in the retrosplenial cortex, especially the superficial layers. It seems likely that this finding is due to the loss of or diminished activity in the direct inputs from the ATN to the RSC (Barnett et al, 2021).…”

The anterior thalamic nuclei: core components of a tripartite episodic memory system

“…One example arises from how deep brain stimulation of the anterior thalamic nuclei in epileptic patients can improve a colour-matching working memory task 168 . Meanwhile optogenetic theta-burst stimulation of the rat anterior thalamic nuclei can rescue the spatial working memory deficit following mammillothalamic tract lesions 215 -findings that yet again underline the significance of these thalamic nuclei for cognition.…”