Propagation of hippocampal ripples to the neocortex by way of a subiculum-retrosplenial pathway

Abstract

Bouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampocortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs.

Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex

“…Given the somewhat surprising depressing nature of anterior thalamic synapses onto LR neurons (compared to the RSG and ACC, we next sought to understand its computational implication with regard to the processing of incoming head direction inputs, particularly as it contrasts with the previously-reported facilitating input from the subiculum (Yamawaki et al, 2019a), another known source of spatial input to LR cells (Figure S3; Nitzan et al, 2020; Yamawaki et al, 2019a). Using a morphologically realistic model of retrosplenial LR cells (Brennan et al, 2020), we investigated how the short-term synaptic dynamics impact the processing of depressing versus facilitating inputs by LR neurons.…”

“…The superficial layers of the granular RSC (RSG) contain two subtypes of principal excitatory pyramidal neurons that have strikingly distinct physiology, morphology, and computational capabilities: the low-rheobase (LR) neuron and the regular-spiking (RS) neuron (Brennan et al, 2020; Kurotani et al, 2013; Yousuf et al, 2020). The RSG receives inputs from many regions, including the anterior thalamus (Ichinohe et al, 2008; O‘Mara, 2013; Shibata, 1993; van Groen and Wyss, 1995; Yamawaki et al, 2019b), subiculum (Yamawaki et al, 2019a, 2019b, Opalka et al, 2020; Nitzan et al, 2020), hippocampus (Alexander et al, 2018; Wyss and van Groen, 1992; Yamawaki et al, 2019b), claustrum (van Groen and Wyss, 2003, 1990; Wang et al, 2017), and cingulate cortex (van Groen and Wyss, 1990, 2003), among others. However, the precise nature of many of these inputs and their relative connectivity with these two distinct superficial subtypes has not yet been documented.…”

Robust information routing by dorsal subiculum neurons

“…While most CA1 (92.7%) and SUB (73.7%) neurons showed significantly (P < 0.01, t-test) higher firing rates during ripple events than during baseline periods, a small fraction of SUB neurons, but not of CA1 neurons, were significantly (P < 0.01, t-test) suppressed during ripples (CA1, 0%; SUB, 4.4%; χ 2 = 14.11, P = 0.0002; Fig. 6C-D) (31). These suppressed neurons were mostly localized in the distal-deep part of the SUB cell layer (Fig.…”

“…SUB projection neurons were also distinctly activated or suppressed during ripples. Due to the widespread projections of the SUB, ripples broadcasted from the SUB might organize the brain-wide activity (38) through the modulation of downstream areas (31,39). Exactly how the distributed information from the SUB is utilized in the target areas remains to be elucidated.…”

Vector Trace cells in the Subiculum of the Hippocampal formation

“…The subiculum is a major output region of the hippocampal formation 17–20 . The subiculum is known to contain vector representations 11 , is implicated in memory retrieval 21–23 , and has recently been identified as likely the hippocampal component of the default mode network 24 . This could suggest a wide role for subicular vector-based representations in directing navigation and memory-based cognition, consistent with models of spatial memory and imagery 8 .…”