The subiculum sensitizes retrosplenial cortex layer 2/3 pyramidal neurons

Abstract

Key points Neurons in the retrosplenial cortex (RSC), a cerebral region that connects synaptically with various brain regions, are known to increase neuronal activity in accordance with hippocampal sharp wave‐ripples. Pyramidal cells in granular RSC (gRSC) layer 2/3, but not layer 5, exhibit slowly ramping depolarization and considerably delayed spikes in response to a step‐pulse current injection. The latencies of delayed spikes in RSC layer 2/3 pyramidal neurons were shortened by a preceding current injection. This effect was mimicked by activation of axonal afferents from the subiculum, but not of neocortical afferents. The subiculum is likely to facilitate information processing and flow in the RSC. Abstract The retrosplenial cortex (RSC), a cerebral region involved in diverse cognitive functions, is an anatomical hub that forms monosynaptic connections with various brain areas. Here, we report a unique form of short‐term intrinsic plasticity in mouse granular RSC layer 2/3 pyramidal cells. These cells exhibited delayed spikes in response to somatic current injection, but the spike latencies were shortened by a preceding brief depolarization (priming). This priming‐induced sensitization is distinct from desensitization, which is commonly observed in other cortical neurons. The facilitatory priming effect lasted for more than 3 s, providing a time window for increased sensitivity to RSC inputs. Based on in vitro and in vivo patch‐clamp recordings following optogenetic stimulation of axonal fibres, we found that preactivation of subicular afferents replicated the facilitatory priming effect. The results suggest that subicular inputs to RSC layer 2/3 neurons may modulate subsequent information integration in the RSC layer 2/3 circuits.

The separate and combined properties of the granular (area 29) and dysgranular (area 30) retrosplenial cortex

“…These projections are inhibitory, with GABAergic CA1 neurons terminating in layer I of area 29, where they help regulate the excitatory inputs from the anterior thalamic nuclei, many of which terminate in the same layer of area 29 (Yamawaki et al, 2019b). In this way they contrast with the glutamatergic subiculum projections that directly excite area 29 pyramidal cells (Yamawaki et al, 2019a;Gao et al, 2021). In addition, area 29 in the rat also receives the large majority of the direct parahippocampal projections from the postsubiculum and presubiculum that reach retrosplenial cortex (Van Groen & Wyss, 1990b,c).…”

Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs spatial memory in the rat

“…These pyramidal cells are distinct from the cell populations influenced by the claustrum and anterior cingulate cortex (Brennan et al, 2021). Additionally, the timing of late neural spikes in layers II and III by the granular retrosplenial pyramidal neurons appears to be influenced by preceding activation of the subiculum (Gao et al, 2021). Together, these findings emphasise the reliance of the three regions on each other, suggesting that together the subiculum and anterior thalamic nuclei facilitate information processing in the retrosplenial cortex, which is gated by its inputs from CA1 (Aggleton & O'Mara, 2022;Yamawaki et al, 2019a).…”

“…Like the hippocampus, retrosplenial cortex is repeatedly implicated in spatial memory and navigation (Nelson et al, 2018;Nelson et al, 2015;Harker & Whishaw, 2004;Vann et al, 2009;Wolbers & Büchel, 2005) as well as episodic memory (Hayashi et al, 2020;Maguire, 2001;Nestor et al, 2003;Vann et al, 2009). Furthermore, recent studies suggest that these subiculum projections may facilitate the flow of contextual information to retrosplenial cortex, thereby enabling memory formation (Gao et al, 2021;Yamawaki et al, 2019b).…”

Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs flexible spatial memory in the rat

“…These pyramidal cells are distinct from the cell populations influenced by the claustrum and anterior cingulate cortex (Brennan et al, 2021). Additionally, the timing of late neural spikes in layers II and III by the granular retrosplenial pyramidal neurons appears to be influenced by the preceding activation of the subiculum (Gao et al, 2021). Together, these findings emphasise the reliance of the three regions on each other, suggesting that together the subiculum and anterior thalamic nuclei facilitate information processing in the retrosplenial cortex, which is gated by its inputs from CA1 (Aggleton & O'Mara, 2022; Yamawaki, Corcoran, et al, 2019).…”