Biology subjects

Lever, C.

Publications and source records attributed to Lever, C..

7 recordsLinked to original sources

bioRxiv2026

Boundary Vector Cells Encode a Future-Biased Spectrum of Positions in the Rat

Spatial tuning is a hallmark property of neural firing in the hippocampal formation. Yet, that tuning is often less well correlated with the instantaneous current position of an animal than it is with an integrated version of the past or future state of the animal. Whether that encoding is biased towards past or future states and the extent to which it shows fixed versus multi-scale encoding varies across circuits and cell types. The temporal encoding properties of boundary vector cells of the subiculum are not well established. To address this here, we re-analyzed recordings of BVCs described previously by Lever et al. (2009) with multiple approaches. In the first, we asked if adding a temporal offset between the rat position and the spiking of a BVC increased the apparent spatial tuning in the firing rate map. We found that aligning BVC spiking with future states maximized the rate map spatial tuning. These results were mirrored in a second analysis that, instead of optimizing rate map spatial tuning, optimized how well the firing rate map predicted the BVC spiking. The second analysis also allowed us to ask whether that encoding is focused on a particular temporal horizon or whether the encoding captures behavior at multiple scales. To this end, for a given recording, we asked "How much time-integration of the behavioral state is the observed spiking most consistent with?" We observed a wide spectrum of time-constants of integration across cells, indicating that BVCs form a multiscale encoding of future states. The distribution of both offsets and integration rates observed across BVCs did not differ significantly from other, non-BVC, subiculum neurons. Taken together, these findings indicate that BVCs, along with other subiculum neurons, form a multi-scale encoding of future states.

neuroscience↗

bioRxiv2024

Unifying Subicular Function: A Predictive Map Approach

The successor representation has emerged as a powerful model for understanding mammalian navigation and memory; explaining the spatial coding properties of hippocampal place cells and entorhinal grid cells. However, the diverse spatial responses of subicular neurons, the primary output of the hippocampus, have eluded a unified account. Here, we demonstrate that incorporating rodent behavioural biases into the successor representation successfully reproduces the heterogeneous activity patterns of subicular neurons. This framework accounts for the emergence of boundary and corner cells - neuronal types absent in upstream hippocampal regions. We provide evidence that subicular firing patterns are more accurately described by the successor representation than a purely spatial or boundary vector cell model of subiculum. Our work reveals a temporal hierarchy in hippocampal-subicular processing, with subiculum encoding predictive representations over longer time horizons than CA1, capturing extended behavioural patterns and environmental affordances.

neuroscience↗

bioRxiv2023

Mice remember experiences via conspecific-context: models of social episodic-like memory

The ability to remember unique past events (episodic memory) may be an evolutionarily conserved function, with accumulating evidence of episodic-(like) memory processing in rodents. In humans, it likely contributes to successful complex social networking. Rodents, arguably the most used laboratory models, are also rather social animals. However, many behavioural paradigms are devoid of sociality, and commonly-used social spontaneous recognition tasks (SRTs) are open to non-episodic strategies based upon familiarity. We address this gap by developing new SRT variants. Here, in object-in-context SRTs, we asked if context could be specified by the presence/absence of either a conspecific (experiment 1) or an additional local object (experiment 2). We show that mice readily used the conspecific as contextual information to distinguish unique episodes in memory. In contrast, no coherent behavioural response emerged when an additional object was used as a potential context specifier. Further, in a new social conspecific-in-context SRT (experiment 3) where environment-based change was the context specifier, mice preferably explored a more recently-seen familiar conspecific associated with contextual mismatch, over a less recently-seen familiar conspecific presented in the same context. The results argue that, in incidental SRT conditions, mice readily incorporate conspecific cue information into episodic-like memory. Thus, the tasks offer different ways to assess and further understand the mechanisms at work in social episodic-like memory processing.

animal behavior and cognition↗

bioRxiv2023

Theta phase precession at encoding predicts subsequent memory of sensory-driven vector fields, & occurs in memory-dependent fields at retrieval

Theta phase precession is thought to confer key computational advantages (e.g. temporal compression suiting spike-timing related plasticity, cognitive relations as phase distances, and population-level coding for directions and sequences). However, direct evidence speaking to: 1) its widely-theorised role in enhancing memorability; 2) its dependence upon sensory input, is lacking. We leveraged the Vector trace cell (VTC) phenomenon to examine these issues. VTCs in subiculum show a simple, unambiguous memory correlate: VTCs remember the distance and direction to a cue after the cue is removed, with a new trace field which was not present before the cue was inserted. Regarding memorability, here we show that subsequently-remembered cue fields (those which become trace fields) exhibit higher levels of phase precession than subsequently-forgotten cue fields (those which produce no trace). Thus, phase precession does appear to enhance memorability, consistent with long-established theory. The second issue concerns the extent of phase precession in sensory-elicited vs memory-dependent firing. Phase precession in CA1 is strongly disrupted following deprivation of its Entorhinal, but not CA3, inputs; this could indicate that theta phase precession is largely sensory-driven and absent in memory-dependent fields. Here, however, we show that phase precession is robust in subicular VTC trace fields, i.e. when the cue that originally elicited the new vector field is no longer present. Thus, the much-theorised benefits of phase precession likely apply to memory-dependent fields. These findings have wide implications for oscillatory-based models of memory.

neuroscience↗

bioRxiv2019

Vector Trace cells in the Subiculum of the Hippocampal formation

Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects, and goals. Cognitive processes such as path-planning and imagination entail recall of vector representations, but evidence of neuron-level memory for allocentric vectors has been lacking. Here we describe a novel neuron type (Vector Trace cell, VTC) whose firing generates a new vector field when a cue is encountered, and also a trace version of that field for hours after cue removal. VTCs are concentrated in subiculum distal to CA1. Compared to non-trace cells, VTCs fire at further distances from cues, and exhibit earlier-going shifts in preferred theta phase in response to newly introduced cues, demonstrating a theta-linked neural substrate for memory encoding. VTCs suggest a vector-based model of computing spatial relationships between an agent and multiple spatial objects, or between different objects, freed from the constraints of direct perception of those objects.

neuroscience↗

bioRxiv2018

Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, and social and anxiety-related behaviours

We studied two new App knock-in mice models of Alzheimers disease (AppNL-F and AppNL-G-F), which generate elevated levels of A{beta}40 and A{beta}42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by A{beta} accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social memory, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: 1) increased thigmotaxis in the Open Field (OF), yet; 2) reduced closed-arm, and increased open-arm, time in the Elevated Plus Maze (EPM). Their ostensibly-anxiogenic OF profile, yet ostensibly-anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. disinhibition), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations, and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble A{beta} overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.\n\nHighlightsO_LIAppNL-G-F KI mice displayed differing anxiety behaviours in two tests of anxiety.\nC_LIO_LIPrefrontal gamma was no longer NMDA-receptor dependent in AppNL-G-F KI mice.\nC_LIO_LIPrefrontal expression of Grin2b was reduced in AppNL-G-F KI mice.\nC_LIO_LIDTI found structural alterations in the hippocampus and prefrontal cortex in AppNL-G-F KI mice.\nC_LI

neuroscience↗

bioRxiv2018

Within-subject combination of diffusion tensor MRI and CLARITY reveals alterations in the social brain network resulting from α-neurexin II deletion

BackgroundOf the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2 knockout (KO) model. MethodsFixed brains of Nrxn2 KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. ResultsDTI revealed decreases in fractional anisotropy and increases in apparent diffusion coefficient in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Radial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2 KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. ConclusionsOur findings demonstrate that deleting a single neurexin gene (Nrxn2) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.

neuroscience↗