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

Abstract

The anterior thalamic nuclei (ATN), a central node in a complex memory system, process spatial and temporal memory. Here, we show that ATN lesions do not affect acquisition of a simple odour discrimination or a simple object discrimination in a runway apparatus. The same procedures were used to test learning of an arbitrary association between non-spatial object-odour pairings (A+X or B+Y were rewarded; but not A+Y or B+X). If ATN lesions recapitulate hippocampal function, specifically CA1 function, then they should disrupt acquisition only when an explicit delay (i.e., a 10-second trace) is inserted between the odour and object. Acquisition was completely abolished by ATN lesions, irrespective of the presence of the temporal trace, and despite extensive training (50x12-trial sessions). Faster acquisition with the 10-second trace was found in the sham-lesion rats. During recall, 5 days after criterion, sham rats but not ATN-lesion rats showed elevated Zif268 expression in hippocampal CA1 for the trace compared to no-trace condition; both sham and lesion rats tested in the trace condition showed increased IEG expression in the superficial layers of the prefrontal cortex and retrosplenial cortex. ATN lesions markedly reduced Zif268 expression in the prefrontal cortex and retrosplenial cortex. This is the first evidence that ATN lesions impair non-spatial paired-associate tasks. The findings suggest that the ATN influence memory beyond time and space, and constitute a critical neural structure for learning arbitrary associations even in the task version that is not disrupted by hippocampal lesions.

Bifurcating Neurons In The Anterior Thalamic Nuclei

“…We suggest that bifurcating AM neurons in particular enable the explicit binding of two or more elements associated with a memory episode that convey different representations across different cortical memory structures. To learn if we are correct will demand non-conventional memory tests that go beyond the classic evidence of the ATN’s role in various aspects of spatial memory and navigation (Aggleton and Nelson, 2015; Dalrymple-Alford et al, 2015; Dupire et al, 2013; Hamilton and Dalrymple-Alford, 2021; Mathiasen et al, 2020; Nelson, 2021; Wolff et al, 2006; Wright 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). The effects of ATN lesions are sometimes more pronounced than lesions that disrupt their individual input or output structures (Dumont et al, 2015; Hamilton and Dalrymple-Alford, 2021; Mitchell et al, 2018; Perry et al, 2018; Warburton et al, 1999). Together, this evidence supports the perspective that the ATN form a critical subcortical hub that actively integrates information processing among telencephalic memory structures (Wolff and Vann, 2019).…”