Biology subjects

Bannerman, D. M.

Publications and source records attributed to Bannerman, D. M..

15 recordsLinked to original sources

bioRxiv2025

Magnetic Fields Influence Visual Responses in Mice

Many animals use the Earths magnetic field for the purposes of orientation and navigation, although the sensory mechanisms remain unclear. It has been proposed that retinal responses to light may be modulated by magnetic fields. However, to date, there is no evidence for a retinal response to magnetic fields in mammals. Here we show that magnetic fields affect expression of the neuronal activity marker c-Fos in the mouse retina in a light dependent manner. These retinal responses to magnetic fields are abolished in mice lacking the candidate magnetoreceptor cryptochrome. To characterise the signalling pathways involved, we then used RNAseq and cell-type mapping. We also show that magnetic fields increase exploratory behaviour in a visually dependent task and lengthen the period of the retinal circadian clock. Together, our data provide the first evidence for a mammalian retinal response to magnetic fields at a cellular, molecular and functional level, which may influence vision.

neuroscience↗

bioRxiv2025

Calcium-permeable AMPAR in hippocampal parvalbumin-expressing interneurons protect against memory interference

Parvalbumin-expressing (PV+) interneurons exert exquisite control over spike output, and plasticity in these inhibitory circuits may be important for maintaining network stability in learning and memory. PV+ interneuron recruitment is primarily mediated by GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPAR), which support anti-Hebbian plasticity. However, the functional significance of CP-AMPAR-mediated plasticity remains unknown. Using a viral approach to artificially express the GluA2 subunit in hippocampal PV+ interneurons, we replaced CP-AMPAR with GluA2-containing receptors, and in doing so reduced synaptically-evoked Ca2+ transients and anti-Hebbian plasticity. Transfection of hippocampal PV+ interneurons with GluA2 resulted in delay-dependent spatial working memory deficits which increased across trials per session, and impaired reversal learning in the Morris water maze but not initial acquisition. Our data suggest that loss of CP-AMPAR-mediated plasticity in these cells leads to proactive interference, revealing a significant role for dynamic recruitment of PV+ interneurons in the segregation of memories and accurate memory retrieval. HighlightsO_LIViral expression of GluA2 in PV+ interneurons alters synaptic AMPA receptor profile C_LIO_LIGluA2 overexpression in PV+ cells reduces synaptic Ca2+ transients and plasticity C_LIO_LIUpregulating GluA2 in PV+ cells causes delay-dependent deficits in working memory C_LIO_LIAcquisition of reference memories is preserved, but reversal learning is impaired C_LI

neuroscience↗

bioRxiv2023

Rebound activation of 5-HT neurons following SSRI discontinuation

Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset, disabling discontinuation syndrome the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus. In microdialysis experiments continuous paroxetine elevated hippocampal extracellular 5-HT and this effect fell to saline control levels on discontinuation. However, depolarisation (high potassium)-evoked 5-HT release was reduced by continuous paroxetine but increased above controls post-discontinuation. Extracellular hippocampal 5-HIAA also decreased during continuous paroxetine and increased above controls post-discontinuation. Next, immunohistochemistry experiments found that paroxetine discontinuation increased Fos expression in midbrain 5-HT neurons, adding further evidence for a hyperexcitable 5-HT system. The latter effect was recapitulated by 5-HT1A receptor antagonist administration although gene expression analysis could not confirm altered expression of 5-HT1A autoreceptors following paroxetine discontinuation. Finally, in behavioural experiments paroxetine discontinuation increased anxiety-like behaviour, which partially correlated in time with the measures of increased 5-HT function. In summary, this study finds that SSRI discontinuation triggers a rebound activation of 5-HT neurons across a range of experiments. This effect is reminiscent of neural changes associated with various psychotropic drug withdrawal states, suggesting a common unifying mechanism.

neuroscience↗

bioRxiv2023

Lasting dynamic effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (+/-)-DOI) on cognitive flexibility

Psychedelic drugs can aid fast and lasting remission from various neuropsychiatric disorders, though the underlying mechanisms remain unclear. Preclinical studies suggest serotonergic psychedelics enhance neuronal plasticity, but whether neuroplastic changes can also be seen at cognitive and behavioural levels is unexplored. Here we show that a single dose of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (({+/-})-DOI) affects structural brain plasticity and cognitive flexibility in young adult mice beyond the acute drug experience. Using ex vivo magnetic resonance imaging, we show increased volumes of several sensory and association areas one day after systemic administration of 2mgkg-1 ({+/-})-DOI. We then demonstrate lasting effects of ({+/-})-DOI on cognitive flexibility in a two-step probabilistic reversal learning task where 2mgkg-1 ({+/-})-DOI improved the rate of adaptation to a novel reversal in task structure occurring one-week post-treatment. Strikingly, ({+/-})-DOI-treated mice started learning from reward omissions, a unique strategy not typically seen in mice in this task, suggesting heightened sensitivity to previously overlooked cues. Crucially, further experiments revealed that ({+/-})-DOIs effects on cognitive flexibility were contingent on the timing between drug treatment and the novel reversal, as well as on the nature of the intervening experience. ({+/-})-DOIs facilitation of both cognitive adaptation and novel thinking strategies may contribute to the clinical benefits of psychedelic-assisted therapy, particularly in cases of perseverative behaviours and a resistance to change seen in depression, anxiety, or addiction. Furthermore, our findings highlight the crucial role of time-dependent neuroplasticity and the influence of experiential factors in shaping the therapeutic potential of psychedelic interventions for impaired cognitive flexibility.

animal behavior and cognition↗

bioRxiv2023

Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioural deficits

Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Yet, our understanding of the functional role of adult oligodendrogenesis remains limited. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice can lead to learning and memory deficits in a range of behavioural tasks. Our results, reported here, have replicated a key finding that learning to run on a complex wheel with unevenly spaced rungs is disrupted by ablation of oligodendrogenesis. However, using ex vivo MRI (MTR and DTI), we also found that ablating oligodendrogenesis by itself alters brain microstructure, independent of behavioural experience. Furthermore, in vivo EEG recording in behaviourally naive mice with ablated oligodendrogenesis revealed altered brain activity in the form of increased EEG power density across a broad frequency range. Together, our data indicate that disrupting the formation of new oligodendrocytes directly alters brain microstructure and activity. This suggests a role for adult oligodendrogenesis in the maintenance of brain function and indicates that task-independent changes to brain structure and function might contribute to the learning and memory deficits associated with oligodendrogenesis ablation.

neuroscience↗

bioRxiv2023

Oscillatory-Quality of sleep spindles: from properties to function

Sleep spindles are traditionally defined as 10-15Hz thalamo-cortical oscillations typical of NREM sleep. While substantial heterogeneity in the appearance or spatio-temporal dynamics of spindle events is well recognised, the physiological relevance of the underlying fundamental property - the oscillatory strength - has not been studied. Here we introduce a novel metric called oscillatory Quality (o-Quality), which is derived by fitting an auto-regressive model to short segments of electrophysiological signals, recorded from the cortex in mice, to identify and calculate the damping of spindle oscillations. We find that the o-Quality of spindles varies markedly across cortical layers and regions and reflects the level of synchrony within and between cortical networks. Furthermore, the o-Quality of spindles varies as a function of sleep-wake history, determines the strength of coupling between spindles and slow waves, and influences the responsiveness to sensory stimulation during sleep. Thus, the o-Quality emerges as a metric that, for the first time, directly links the spatio-temporal dynamics of sleep spindles with their functional role.

neuroscience↗

bioRxiv2023

Oligodendrocyte dynamics dictate individual performance outcomes of working memory training in mice

Motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursors (OLPs). We asked whether OL production is also required for non-motor learning and cognition, using T-maze and radial arm maze tasks that tax spatial working memory. Maze training stimulated OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation; myelin sheath formation was also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impaired training-induced improvements in maze performance. Remarkably, there was a strong positive correlation between working memory performance of individual mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in the mPFC, underscoring the key role of OL lineage cells in cognitive performance.

neuroscience↗

bioRxiv2022

"Paradoxical wakefulness" induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the cortex concomitant with pupillometry in freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). We observed an acute induction of a dissociated state of arousal, characterised by prominent sleep-like slow waves in the cortex and marked pupil dilation in behaviourally awake, moving animals. REM sleep was markedly suppressed, similar to the effect of conventional antidepressants. We argue that the occurrence of a dissociated brain state combining features of waking and sleep may fundamentally underpin the known and hypothesised effects of psychedelics -- from dream-like hallucinations to reopening of the critical period for plasticity.

neuroscience↗

bioRxiv2021

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience.

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the aetiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1-/-) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1-/- mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1-/- mice. Furthermore, dopamine signals were initially similar in Gria1-/- mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1-/- mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia.

neuroscience↗

bioRxiv2021

Retrosplenial cortex is necessary for spatial and non-spatial latent learning in mice

Latent learning occurs when associations are formed between stimuli in the absence of explicit reinforcement. Traditionally, latent learning in rodents has been associated with the creation internal models of space. However, increasing evidence points to roles of internal models also in non-spatial decision making. Whether the same brain structures and processes support the creation of spatially-anchored or non-spatial internal models via latent learning, is an open question. To address this question, we developed a novel operant box task that allows to test spatial and non-spatial versions of a flavour-based sensory preconditioning paradigm. We probed the role of the retrosplenial cortex, a brain area associated with spatial cognition and subjective value representation, in this task using precise, closed-loop optogenetic silencing during different task phases. We show that the retrosplenial cortex is necessary for both spatial and non-spatial latent learning in mice. We further demonstrate that the requirement of retrosplenial cortex is limited to the preconditioning phase of the task. Our results provide insight into the specific role of the retrosplenial cortex in latent learning, demonstrate that latent learning plays a general part in the creation of internal models, independent of spatial anchors, and provide a novel avenue for studying model-based decision making.

neuroscience↗

bioRxiv2021

Effect of SSRI discontinuation on anxiety-like behaviours in mice

BackgroundAbrupt cessation of therapy with a selective serotonin reuptake inhibitor (SSRI) is associated with a discontinuation syndrome, typified by numerous disabling symptoms including anxiety. Surprisingly little is known of the behavioural effect of SSRI discontinuation in animals. AimHere, the effect of SSRI discontinuation on anxiety-like behaviour was systematically investigated in mice. MethodsExperiments were based on a 3-arm experimental design comprising saline, continued SSRI and discontinued SSRI. Mice were assessed 2 days after SSRI discontinuation over a 5 day period using the elevated plus maze (EPM) and other anxiety tests. ResultsAn exploratory experiment found cessation of paroxetine (12 days) was associated with decreased open arm exploration and reduced total distance travelled, in male but not female mice. Follow-up studies confirmed a discontinuation effect on the EPM in male mice after paroxetine (12 days) and also citalopram (12 days). Mice receiving continued paroxetine (but not citalopram) also showed decreased open arm exploration but this was dissociable from effects of discontinuation. The discontinuation response to paroxetine did not strengthen after 28 days treatment but was absent after 7 days treatment. A discontinuation response was not decernable in other anxiety and fear-learning tests applied 3-5 days after treatment cessation. Finally, discontinuation effects on the EPM were typically associated with decreased locomotion on the test. However, separate locomotor testing implicated anxiety-provoked behavioural inhibition rather than a general reduction in motor activity. ConclusionOverall, the current study provides evidence for a short-lasting behavioural discontinuation response to cessation of SSRI treatment in mice.

neuroscience↗

bioRxiv2021

Highly task-specific and distributed neural connectivity in working memory revealed by single-trial decoding in mice and humans

Working memory (WM), the capacity to briefly and intentionally maintain mental items, is key to successful goal-directed behaviour and impaired in a range of psychiatric disorders. To date, several brain regions, connections, and types of neural activity have been correlatively associated with WM performance. However, no unifying framework to integrate these findings exits, as the degree of their species- and task-specificity remains unclear. Here, we investigate WM correlates in three task paradigms each in mice and humans, with simultaneous multi-site electrophysiological recordings. We developed a machine learning-based approach to decode WM-mediated choices in individual trials across subjects from hundreds of electrophysiological measures of neural connectivity with up to 90% prediction accuracy. Relying on predictive power as indicator of correlates of psychological functions, we unveiled a large number of task phase-specific WM-related connectivity from analysis of predictor weights in an unbiased manner. Only a few common connectivity patterns emerged across tasks. In rodents, these were thalamus-prefrontal cortex delta- and beta-frequency connectivity during memory encoding and maintenance, respectively, and hippocampal-prefrontal delta- and theta-range coupling during retrieval, in rodents. In humans, task-independent WM correlates were exclusively in the gamma-band. Mostly, however, the predictive activity patterns were unexpectedly specific to each task and always widely distributed across brain regions. Our results suggest that individual tasks cannot be used to uncover generic physiological correlates of the psychological construct termed WM and call for a new conceptualization of this cognitive domain in translational psychiatry.

neuroscience↗

bioRxiv2020

Waking experience modulates sleep need in mice

Homeostatic regulation of sleep is reflected in the maintenance of a daily balance between sleep and wake. Although numerous internal and external factors can influence sleep, it is unclear whether and to what extent the process that keeps track of time spent awake is determined by the content of the waking experience. We hypothesised that alterations in environmental conditions may elicit different types of wakefulness, which will in turn influence both the capacity to sustain continuous wakefulness as well the rates of accumulating sleep pressure. To address this, we performed two experiments, where we compared wakefulness dominated by novel object exploration with either (i) the effects of voluntary wheel running (Experiment 1) or (ii) performance in a simple touchscreen task (Experiment 2). We find that voluntary wheel running results in longer wake episodes, as compared with exploratory behaviour; yet it does not lead to higher levels of EEG slow wave activity (SWA) during subsequent sleep. On the other hand, engagement in a touchscreen task, motivated by a food reward, results in lower SWA during subsequent sleep, as compared to exploratory wakefulness, even though the total duration of wakefulness was similar. Overall, our study suggests that sleep-wake behaviour is highly flexible within an individual, and that the homeostatic process that keeps track of time spent awake is sensitive to the nature of the waking experience. We therefore conclude that sleep dynamics are determined, to a large degree, by the interaction between the organism and the environment.

neuroscience↗

bioRxiv2019

Skill acquisition increases myelination and strengthens functional connectivity in the sensorimotor circuit of the adult rat

The effects of skill acquisition on whole-brain structure and functional networks have been extensively investigated in humans but have yet to be explored in rodents. Forelimb reaching training in rodents results in well-established focal functional and structural reorganization within the motor cortex (M1) and cerebellum, indicating distributed alterations in both structure and function. However, it is unclear how local alterations in structure and function relate to distributed learning-related changes across motor networks. Here we trained adult rats in skilled reaching and used multimodal whole-brain in vivo MRI to assess both structural and functional plasticity over time.\n\nWe detected increases in a myelin-related MRI metric in white matter, cortical areas, and to a lesser extent in the cerebellum, paralleled by strengthened functional connectivity between M1 and cerebellum, possibly reflecting a decrease in cerebellum inhibition over M1. Skill learning therefore leads to myelin increases in pathways that connect sensorimotor regions, and in functional connectivity increases between areas involved in motor learning, all of which correlate with performance. These findings closely mirror previous reports of network-level changes following motor learning in humans and underlines the correspondence between human and rodent brain circuits for motor learning, despite important differences in the anatomy of physiology of movement circuits between species.

neuroscience↗

bioRxiv2017

Discriminative aversive learning and amygdala responsivity is enhanced in mice with reduced serotonin transporter activity

The serotonin (5-HT) transporter (5-HTT) regulates 5-HT availability at the synapse. Low or null 5-HTT expression results in increased 5-HT availability and has been reported to produce anxious and depressive phenotypes, although this remains highly controversial despite two decades of investigation. Paradoxically, SSRIs, which also increase 5-HT availability, reduce the symptoms of anxiety and depression. An emerging network plasticity theory of 5-HT function argues that, rather than influencing mood directly, increasing 5-HT availability enhances learning about emotionally-significant events but evidence supporting this theory is inconclusive. Here, we tested one key prediction of this theory: that increased 5-HT availability enhances aversive learning. In experiment 1, we trained 5-HTT knock-out mice (5-HTTKO), which have increased 5-HT availability, and wild-type mice (WT) on an aversive discrimination learning task in which one auditory cue was paired with an aversive outcome whereas a second auditory cue was not. Simultaneously we recorded neuronal and hemodynamic responses from the amygdala, a brain region necessary for aversive learning. 5-HTTKO mice exhibited superior discrimination learning than WTs, and had stronger theta-frequency neuronal oscillations and larger amygdala hemodynamic responses to the aversive cues, which predicted the extent of learning. In experiment 2, we found that acute SSRI treatment (in naive non-transgenic mice), given specifically before fear learning sessions, enhanced subsequent fear memory recall. Collectively, our data demonstrate that reducing 5-HTT activity (and thereby increasing 5-HT availability) enhances amygdala responsivity to aversive events and facilitates learning for emotionally-relevant cues. Our findings support the network plasticity theory of 5-HT function.

neuroscience↗