Biology subjects

Dachtler, J.

Publications and source records attributed to Dachtler, J..

4 recordsLinked to original sources

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

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats

Excessive consumption of high fat and high sugar (HFHS) diets are known to alter reward processing and aspects of behaviour, and change microbiota profiles. Studies in gnotobiotic mice also provide evidence that gut microorganisms influence social behaviour. To further investigate these interactions, the impact of intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition was examined. Rats were permitted intermittent daily access (2h / day) to a palatable HFHS diet for 28 days across the adolescent period. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. Reduced social interaction behaviours, and impaired social memory and novel object recognition were observed in HFHS diet rats. Reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA were observed in the PFC of HFHS diet rats. The relative abundance of a number of specific taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria, which also predicted social behaviours, novel object recognition performance and Maoa expression. This is the first study to show that limited daily access to HFHS diet alters social behaviour and cognition in rats. Furthermore, behavioural changes are associated with alterations to cortical gene expression of enzymes involved in monoamine synthesis and neuroplasticity, and microbiota profiles predicted diet-induced changes to behaviour and gene expression.

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↗