A thalamic reticular circuit for head direction cell tuning and spatial navigation

Abstract

A thalamic reticular circuit 1 for head direction cell tuning 2 and spatial navigation 3 4 Summary 11To navigate in space, an animal must reference external sensory landmarks to the spatial 12 orientation of its body and head. Circuit and synaptic mechanisms that integrate external cues 13 with internal head-direction (HD) signals to drive navigational behavior remain, however, poorly 14 described. We identify an excitatory synaptic projection from the presubiculum and retrosplenial 15 cortex to the anterodorsalmost sector of the thalamic reticular nucleus (TRN), so far classically 16 implied in gating sensory information flow. Projections to TRN showed driver characteristics and 17 involved AMPA/NMDA-type glutamate receptors that initiated TRN cell burst discharge and 18 feedforward inhibition of anterior thalamic nuclei, where HD-tuned cells relevant for egocentric 19 navigation reside. Chemogenetic anterodorsal TRN inhibition broadened the tuning of thalamic 20 HD cells and compromised egocentric search strategies in the Morris water maze. Besides 21 sensory gating, TRN-dependent thalamic inhibition is an integral part of limbic navigational circuits 22to recruit HD-cell-dependent search strategies during spatial navigation. 23 P a g e | 3 (RSC) (Clark et al., 2010). Both areas are reciprocally connected (van Groen and Wyss, 1990) 60 and receive afferents from ATN, primary and secondary visual cortex, integrating information 61 relevant for egocentric and allocentric, external cue-guided, navigation (Dumont and Taube, 2015; 62 Clark et al., 2018;Mitchell et al., 2018;Simonnet and Fricker, 2018). Behaviorally, lesion of dPreS 63 compromises rapid orienting behaviors based on landmarks (Yoder et al., 2019), whereas RSC 64 lesions lead to multiple deficits in spatial navigation and memory formation (Clark et al., 2018; 65 Mitchell et al., 2018). Although there is evidence for a topographically organized cortical feedback 66 from RSC to rat and monkey anterodorsal TRN (Cornwall et al., 1990;Lozsádi, 1994; Zikopoulos 67 and Barbas, 2007), the nature of this cortico-thalamic communication has never been 68 characterized. Indeed, current models of HD circuits involving ATN, dPreS and RSC (Dumont 69 and Taube, 2015;Peyrache et al., 2017;Simonnet and Fricker, 2018; Perry and Mitchell, 2019) 70 and of the brain's 'limbic ' navigational system (Bubb et al., 2017) largely disregard a functionally 71 integrated TRN. In spite of this gap of knowledge, the notion of a limbic anterior TRN has been 72 proposed recently (Zikopoulos and Barbas, 2012;Halassa et al., 2014). 73In this study, we combined tracing techniques, in vitro and in vivo electrophysiological recordings 74 together with a spatial navigation task to probe the synaptic integration and the function of TRN 75 in the communication between PreS, RSC and ATN. 76 77 Results 78 RSC and PreS send topographically organized projections to ATN and TRN 79To determine afferent projection to the anterodorsal portion of the TRN, we injected small volumes 80 (5...

A compact spatial map in V2 visual cortex

“…Vision supports spatial navigation by providing distal visual cues and identifying visual landmarks (Flossmann and Rochefort, 2020; Nau et al, 2018; Saleem, 2020). It has been shown that visual thalamic and cortical neurons are modulated by spatial signals in both virtual and naturalistic environments (Diamanti et al, 2021; Fiser et al, 2016; Fournier et al, 2020; Hok et al, 2018; Jankowski and O’Mara, 2015; Leinweber et al, 2017; Pakan et al, 2018; Saleem et al, 2013; Saleem et al, 2018; Taube, 1995; Vantomme et al, 2020). Spatial representations discovered in multiple visual areas is not surprising since the visual system is responsible for transforming sensory information from eye-centered to world-centered coordinates and estimating self-location (Fournier et al, 2020).…”

“…Meanwhile, all physical location-based spatial cell types have their corresponding visual analogues, which include spatial view cells, saccade direction cells, visual grid and border cells that have been reported in the monkey and human hippocampal-entorhinal network (Doeller et al, 2010; Julian et al, 2018; Killian et al, 2012; Killian et al, 2015; Nau et al, 2018; Rolls and O’Mara, 1995). Spatial tuning has been established in the dorsal lateral geniculate nucleus (dLGN), V1 and other visual cortical areas along the visual pathway from head-fixed as well as freely foraging animals during spatial navigation tasks (Diamanti et al, 2021; Fiser et al, 2016; Fournier et al, 2020; Hok et al, 2018; Jankowski and O’Mara, 2015; Leinweber et al, 2017; Pakan et al, 2018; Saleem et al, 2013; Saleem et al, 2018; Siegle et al, 2021; Taube, 1995; Vantomme et al, 2020). Recent experimental findings have shown that similar hippocampal-entorhinal network mechanisms supporting navigation also mediate a world- centered representation of visual space (Nau et al, 2018).…”

Noradrenergic circuit control of non-REM sleep substates

“…For optogenetic experiments, DBH-Cre animals were implanted with custom-made optic fibers. 69 A multimode fiber (225 m outer diameter, Thorlabs, BFL37-2000/FT200EMT) was inserted and glued (heat-curable epoxy, Precision Fiber Products, ET-353ND-16OZ) to a multimode ceramic zirconia ferrule (Precision Fiber Products, MM-FER2007C-2300). The penetrating end was cut at the desired length with a carbide-tip fiber optic scribe (Precision Fiber Products, M1-46124).…”

“…Thalamic brain slice recordings were performed as previously described in detail. 21,69 Briefly, 3 -6 weeks after viral injection, DBH-Cre mice aged 8 -16 weeks were subjected to isoflurane anesthesia, after which they were decapitated, brains extracted and quickly immersed in ice-cold oxygenated sucrose solution (which contained in mM): NaCl 66, KCl 2.5, NaH2PO4 1.25, NaHCO3 26, D-saccharose 105, Dglucose 27, L(+)-ascorbic acid 1.7, CaCl2 0.5 and MgCl2 7), using a sliding vibratome (Histocom). Brains were trimmed at the level of the brainstem, glued on the trimmed surface on an ice-cold metal blade and apposed to a supporting agar block on their ventral side.…”

Neurophysiological coding of space and time in the hippocampus, entorhinal cortex, and retrosplenial cortex

“…Other RSC HD neurons exhibit tuning anchored to local visual landmarks (Jacob et al, 2017). The conditions sufficient to produce this form of directional tuning are still being explored (Zhang and Jeffery, 2019) but the existence of locally anchored HD tuning could prove important for anchoring the broader HD network to the constellation of distal cues that define space within the external world (Bicanski and Burgess, 2016; Clark et al, 2010; Vantomme et al, 2020). HD cells in either PPC or RSC comprise roughly 10% of the population, although there is variability across studies.…”