Retrograde and anterograde contextual fear amnesia induced by selective elimination of layer IV-Va neurons in the granular retrosplenial cortex (A29)

Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex

“…Our results reproduce these observations ( Figure 2—figure supplement 1 ). Layer 5 is not a homogenous layer, often divided into sublayers 5A and 5B ( Sempere-Ferràndez et al, 2019 ; Sempere-Ferràndez et al, 2018 ; Sigwald et al, 2020 ; Sripanidkulchai and Wyss, 1987 ; Yamawaki et al, 2016a ) and contains a variety of pyramidal cells, including the thin-tufted and thick-tufted neurons who have been shown to exhibit different responses to external inputs ( Sempere-Ferràndez et al, 2018 ; Wyss et al, 1990 ). Further work is needed to determine whether any particular subtype of layer five pyramidal neurons may exhibit substantial TC-evoked responses, but our results, reporting significantly larger responses to TC input by LR neurons, suggest LR cells are the predominant spatial information-encoding subtype within RSG.…”

Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex

“…This suggests precise modulation and coordination of fear signals converging in RSC, establishing retrosplenial circuits as a crucial computational endpoint in certain fear-conditioning behaviors. Indeed, studies have shown that the RSC, and not the amygdala, is necessary for trace fear-conditioning and extinction (Kwapis et al, 2014), and retrosplenial damage results in impaired fear memory (Sigwald et al, 2020; Todd et al, 2017). The ACC is similarly implicated in trace fear-conditioning (Han et al, 2003; Steenland et al, 2012; Vetere et al, 2011; Zhao et al, 2006), and its interactions with the RSC may partly facilitate the encoding and early retrieval of novel fear associations (Corcoran et al, 2016).…”

“…This precise sublaminar organization results in control of RS, but not LR, neurons by CLA and ACC signaling, suggesting that RS neurons may be the predominant cell type underlying the retrosplenial role in fear processing. Indeed, elimination of so-called “layer 4” RS cells in RSG results in contextual fear amnesia (Sigwald et al, 2020), implying that these layer 4 RS cells, which, due to the controversial nature of the RSG layer 4 described below, may overlap with our deep layer 3 RS cells, are the key cell type facilitating contextual fear-conditioning in the RSC. Thus, the precise organization of RSG neurons and inputs facilitates the functional specification of neighboring principal neuron subtypes, with LR neurons underlying the RSC’s navigational functions and RS cells underlying its contextual fear functions.…”

“…Our results reproduce these observations (Figure 2 - figure supplement 1). Layer 5 is not a homogenous layer, often divided into sublayers 5A and 5B (Sempere-ferràndez et al, 2019; Sempere-Ferràndez et al, 2018; Sigwald et al, 2020; Sripanidkulchai and Wyss, 1987; Yamawaki et al, 2016a), and contains a variety of pyramidal cells, including the thin-tufted and thick-tufted neurons who have been shown to exhibit different responses to external inputs (Sempere-Ferràndez et al, 2018; Wyss et al, 1990). Further work is needed to determine whether any particular subtype of layer 5 pyramidal neurons may exhibit substantial TC-evoked responses, but our results, reporting significantly larger responses to TC input by LR neurons, suggest LR cells are the predominant spatial information-encoding subtype within RSG.…”

“…Indeed, a recent study reported that selective ablation of putative retrosplenial RS cells located near the boundary and within upper layer 5 resulted in contextual fear amnesia (Sigwald et al, 2020), indicating that these cells are involved in the fear-related functions of the retrosplenial cortex (Lukoyanov and Lukoyanova, 2006; Yamawaki et al, 2019a, 2019b). The laminar location of these cells corresponds well to the position of the RS cells recorded in our study that we show to preferentially receive CLA and ACC inputs.…”