Tobias Bast

University of Nottingham | Notts · School of Psychology

Investigating how, when, and what subjects learn during decision-making tasks requires tracking their choice strategies on a trial-by-trial basis. Here we present a simple but effective probabilistic approach to tracking choice strategies at trial resolution using Bayesian evidence accumulation. We show this approach identifies both successful lear...

In this issue, Griesius et al report that heterozygous Dlg2+/‐ rats showed a reversal learning impairment on a specific bowl‐digging task, whereas other reversal tasks were unaffected. The study suggests that Dlg2 gene disruption, which has been linked to neuropsychiatric disorders, including schizophrenia, may cause relatively specific impairments...

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but the neurophysiological mechanisms underlying the regulation of CFC by neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this circuit regulate CFC and local synaptic plasticity, which is facilitate...

Animal models are important in preclinical psychopharmacology to study mechanisms and potential treatments for psychiatric disorders. A working group of 14 volunteers, comprising an international team of researchers from academia and industry, convened in 2021 to discuss how to improve the translational relevance and interpretation of findings from...

Importance: Although professional soccer players appear to be at higher risk of neurodegenerative disease, the reason remains unknown. Objective: To examine whether heading frequency is associated with risk of cognitive impairment in retired professional soccer players. Design, setting, and participants: A UK nationwide cross-sectional study w...

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but the neurophysiological mechanisms underlying the regulation of CFC by neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this circuit regulate CFC and local synaptic plasticity, which is facilitate...

Background Previous studies based on death certificates have found professional soccer players were more likely to die with neurodegenerative diseases, including dementia. Therefore, this study aimed to investigate whether retired professional male soccer players would perform worse on cognitive tests and be more likely to self-report dementia diag...

Schizophrenia has been associated with both hypofrontality (i.e., reduced prefrontal cortex (PFC) activation) and prefrontal disinhibition (i.e., reduced GABAergic neural inhibition). Additionally, schizophrenia is characterised by marked reversal learning deficits. Reversal learning has mainly been found to require the orbitofrontal (OFC), but not...

Reversal learning is a form of cognitive flexibility, and involves switching from one response to another when the reward contingencies of the responses are reversed. Recently, we found that medial prefrontal cortex (mPFC) disinhibition by the GABA-A receptor antagonist picrotoxin markedly impaired repeated reversal learning performance in rats. m...

Although chronic pain states have been associated with impaired cognitive functions, including memory and cognitive flexibility, the cognitive effects of osteoarthritis (OA) pain remain to be clarified. The aim of this study was to measure cognitive function in the mono-iodoacetate (MIA) rat model of chronic OA-like knee pain. We used young adult m...

Investigating the strategies engaged by subjects in decision making and learning requires tracking their choice strategies on a trial-by-trial basis. Here we present a simple but effective probabilistic approach to tracking choice strategies at trial resolution, using Bayesian evidence accumulation. We show this approach identifies both successful...

Although chronic pain states have been associated with impaired cognitive functions, including memory and cognitive flexibility, the cognitive effects of osteoarthritis (OA) pain remain to be clarified. The aim of this study was to measure cognitive function in the mono-iodoacetate (MIA) rat model of chronic OA-like knee pain. We used young adult m...

Introduction Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neuro...

Previous research has established links between chronic pain and impaired cognitive ability, as well as between chronic pain and anxiety, in osteoarthritis. Furthermore, there is evidence linking risk of osteoarthritis to lower educational attainment. However, the inter-play of these factors with key social factors (e.g., social deprivation) at the...

Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Conseq...

Background: The transgenic TgF344-AD (TG) rat is emerging as a useful model for investigating age-dependent AD features that include behavioural, electrophysiological and pathological phenotypes of relevance to disease. In this study we investigated changes related to early stages of AD in 9 month old animals. Method: Male and female TG rats and...

There is currently no brain atlas available to specifically determine stereotaxic coordinates for neurosurgery in Lister hooded rats despite the popularity of this strain for behavioural neuroscience studies in the United Kingdom and elsewhere. We have created a dataset, which we refer to as ‘Ratlas-LH’ (for Lister hooded). Ratlas-LH combines in vi...

Hippocampal neural disinhibition, i.e. reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signalling, which play a role in salience modulation. Theref...

Spatial memory has been closely related to the medial temporal lobe and theta oscillations are thought to play a key role. However, it remains difficult to investigate medial temporal lobe activation related to spatial memory with non-invasive electrophysiological methods in humans. Here, we combined the virtual delayed-matching-to-place task, reve...

Humans and non-human animals show great flexibility in spatial navigation, including the ability to return to specific locations based on as few as one single experience. To study spatial navigation in the laboratory, watermaze tasks, in which rats have to find a hidden platform in a pool of cloudy water surrounded by spatial cues, have long been u...

Background Links between pain and cognitive function on one hand and pain and anxiety on the other have already been shown in other studies and there is biological evidence linking osteoarthritis to educational attainment. However, the inter-play of these factors and the role of key social (social deprivation) factors at the early disease stages ar...

Previous research established links between pain and cognitive function on one hand and pain and anxiety on the other, and there is some evidence linking osteoarthritis to lower educational attainment. However, the inter-play of these factors and the role of key social factors (social deprivation) at the early disease stages are not understood. Usi...

Humans and non-human animals show great flexibility in spatial navigation, including the ability to return to specific locations based on as few as one single experience. To study spatial navigation in the laboratory, watermaze tasks, in which rats have to find a hidden platform in a pool of cloudy water surrounded by spatial cues, have long been u...

Spatial memory has been closely related to the medial temporal lobe (MTL), and theta-oscillations are thought to play a key role. However, it remains difficult to investigate medio-temporal lobe (MTL) activation related to spatial memory with non-invasive electrophysiological methods in humans. Here, we combined the virtual delayed-matching-to-plac...

Reduced inhibitory GABA function, so‐called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age‐related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA‐A receptor antagonist picrotoxin disrupted memory and attention and enhanced hippocamp...

Reduced inhibitory GABA function, so-called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA-A antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi-...

« Mais où ai-je garé ma voiture ? Pourquoi suis-je étourdi ce matin ? Mon cerveau n'est pas réveillé ! » Longtemps, on a cru que des troubles cognitifs et de nombreuses maladies mentales étaient dus à une activité cérébrale insuffisante. En fait, c'est le contraire : un manque d'inhibition, donc un trop-plein d'excitation neuronale, est à l'origine...

HIRNFORSCHUNG NEURONALE HEMMUNG Lange Zeit dachten Forscher, dass viele neurologische und psychiatrische Erkrankungen auf einer zu geringen Hirnaktivität beruhen. Doch häufig ist genau das Gegenteil der Fall. Weniger ist manchmal mehr!

Rationale Dopamine D1 receptor (D1R) signalling is involved in contextual fear conditioning. The D1R antagonist SCH23390 impairs the acquisition of contextual fear when administered systemically or infused locally into the dorsal hippocampus or basolateral amygdala. Objectives We determined if state dependency may account for the impairment in con...

Cover legend: This cover image is based on the Research Article. A new human delayed‐matching‐to‐place test in a virtual environment reverse‐translated from the rodent watermaze paradigm: characterization of performance measures and sex differences, by Matthew G. Buckley and Tobias Bast, DOI: 10.1002/hipo.22992.

Watermaze tests of place learning and memory in rodents, and corresponding reverse translated human paradigms in real or virtual environments, are key tools to study hippocampal function. In common variants, the animal or human participant has to find a hidden goal that remains in the same place over many trials, allowing for incremental learning o...

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunct...

Subconvulsive hippocampal neural disinhibition, that is reduced GABAergic inhibition, has been implicated in neuropsychiatric disorders characterized by attentional and memory deficits, including schizophrenia and age-related cognitive decline. Considering that neural disinhibition may disrupt both intra-hippocampal processing and processing in hip...

Hippocampal lesions tend to facilitate two way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side...

Dopamine D1-like receptor signalling is involved in contextual fear conditioning, but the brain regions involved and its role in other contextual fear memory processes remain unclear. The objective of this study was to investigate (1) the effects of SCH 23390, a dopamine D1/D5 receptor antagonist, on contextual fear memory encoding, retrieval and r...

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbala...

The watermaze delayed matching-to-place (DMP) task was modified to include probe trials, to quantify search preference for the correct place. Using a zone analysis of search preference, a gradual decay of one-trial memory in rats was observed over 24 h with weak memory consistently detected at a retention interval of 6 h, but unreliably at 24 h. Th...

Studies in rats, involving hippocampal lesions and hippocampal drug infusions, have implicated the hippocampus in the modulation of anxiety-related behaviors and conditioned fear. The ventral hippocampus is considered to be more important for anxiety- and fear-related behaviors than the dorsal hippocampus. In the present study, we compared the role...

Consistent with the requirement of D1-class dopamine receptors for the induction of late (>3 h) hippocampal long-term potentiation (LTP), hippocampus-dependent 1-trial memory at long retention delays (>6 h) requires hippocampal D1-class receptors during learning. Hippocampal D1-class receptors also modulate the induction and magnitude of early LTP...

How is hippocampal learning, including place learning, translated into behavior? The hippocampus integrates, along its septotemporal axis, substrates of rapid place learning, including entorhinal-hippocampal connectivity, with functional connectivity to subcortical sites and prefrontal cortex, which play central roles in behavioral-control function...

Manganese (Mn(2+))-enhanced magnetic resonance (MR) imaging (MEMRI) in rodents offers unique opportunities for the longitudinal study of hippocampal structure and function in parallel with cognitive testing. However, Mn(2+) is a potent toxin and there is evidence that it can interfere with neuronal function. Thus, apart from causing adverse periphe...

Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along...

Firing Properties of Complex Spike Cells in Septal CA1 Recorded from Control Rats with an Intact Hippocampus and from Rats with Partial Hippocampal Lesions Sparing Only the Septal Pole (105 KB DOC)

Experiment 2: Performance on the Incremental Place-Learning Task across All Days and Trials (A) Path lengths (mean ± SEM) to reach the platform on the eight daily trials (T1–T8) of days 1–5 and on the single trial on day 6. (B) Percentage time (%time) in correct zone (mean ± SEM; chance level 12.5%, indicated by stippled line) on the trials that we...

Experiment 2: Path Lengths and Savings during Retesting on the Rapid Place-Learning Task Only sham-operated rats and the group with hippocampal lesions sparing the intermediate region showed a significant reduction in path lengths from trial 1 to 2 (t > 3.54, p < 0.001; all other t < 1.23, p > 0.24), i.e., savings (group × trial interaction for pat...

Experiment 4: Firing-Rate and Path Maps for All Cells Recorded from Septal CA1 during a Succession of 15-min Trials in the Familiar Environment (Fam) and the New Environment (New) Recordings from hippocampal residuals at the septal pole, left, and from an intact hippocampus, right, are shown. The color-coded firing-rate maps and, below, the locatio...

Experiment 5: Postsurgical Performance on the Rapid Place-Learning Task with a 15- to 30-s or a 20-min Delay between Trials 1 and 2 (A) Percentage time (%time) in the correct zone (mean ± SEM; chance level 12.5%, indicated by stippled line) when trial 2 was conducted as a probe trial either 15–30 s or 20 min after trial 1 (one probe per delay). The...

The Supporting Text containing Supplementary Results, Supplementary Discussion, Supplementary Materials and Methods, and Supplementary References (86 KB DOC)

Hippocampal Residual in the Intermediate Region (2.20 MB MOV)

Experiment 4: Firing-Rate and Path Maps for All Cells Recorded from Septal CA1 during Two Successive Recording Trials in the Familiar Environment (Fam) Recordings from rats with hippocampal residuals at the septal pole (A) and from rats with an intact hippocampus (B) are shown. The color-coded firing-rate maps and, below, the location of spikes (re...

Platform Locations Used During the Different Stages of Behavioral Testing and the Surrounding Zones Used for the Analysis of Search Preference (96 KB PDF)

Stereotaxic Coordinates (in Millimeters from Bregma) and Injection Volumes for the Hippocampal Ibotenic Acid Injections in the Different Lesion Groups (53 KB DOC)

Intact Hippocampus Videos S1–S5 show rotations of the 3D reconstructions depicted in Figures 1C and 6B; please note that, different from the figures, hippocampal residuals are not overlaid on an intact hippocampus. (2.24 MB MOV)

Experiment 1: Pretraining Performance in the Five Prospective Surgical Groups at the Two Different Retention Delays between Trials 1 and 2 The prospective surgical groups, to receive different hippocampal lesions or sham surgery (see Figure 1C), were matched for: (A) percentage time (%time) in correct zone (mean ± SEM; chance level 12.5%, indicated...

Experiment 1: Postsurgical Performance on the Rapid Place-Learning Task with a 15- to 30-s or a 20-min Delay between Trials 1 and 2 (A) Percentage time (%time) in the correct zone (mean ± SEM; chance level 12.5%, indicated by stippled line) when trial 2 was conducted as a probe trial either 15–30 s or 20 min after trial 1 (one probe per delay). Apa...

Experiment 5: Presurgical Training on the Rapid Place-Learning Task and Performance Matching (A) Latencies (mean ± SEM) to reach the platform on the four daily trials across the 8 d of presurgical training (data are shown for the 23 rats that were included in the final analysis). Data were collapsed for the two different delays between trial 1 and...

Hippocampal Residual at the Temporal Pole (2.44 MB MOV)

Hippocampal Residual at the Septal Pole (2.66 MB MOV)

Hippocampal Residuals at the Temporal and Septal Tip Following Selective Lesion of the Intermediate Region (2.92 MB MOV)

The mammalian hippocampus has been associated with learning and memory, as well as with many other behavioral processes. In this article, these different perspectives are brought together, and it is pointed out that integration of diverse functional domains may be a key feature enabling the hippocampus to support not only the encoding and retrieval...

Allocentric place memory may serve to specify the context of events stored in human episodic memory. Recently, our laboratory demonstrated that, analogous to event-place associations in episodic memory, rats could associate, within one trial, a specific food flavor with an allocentrically defined place in an open arena. Encoding, but not retrieval,...

Many behavioral functions-including sensorimotor, attentional, memory, and emotional processes-have been associated with hippocampal processes and with dopamine transmission in the medial prefrontal cortex (mPFC). This suggests a functional interaction between hippocampus and prefrontal dopamine. The anatomical substrate for such an interaction is...

The amnestic effects of hippocampal lesions are well documented, leading to numerous memory-based theories of hippocampal function. It is debatable, however, whether any one of these theories can satisfactorily account for all the consequences of hippocampal damage: Hippocampal lesions also result in behavioural disinhibition and reduced anxiety. A...

While the hippocampus makes unique contributions to memory, it has also long been associated with sensorimotor processes, i.e. innate processes involving control of motor responses to sensory stimuli. Moreover, hippocampal dysfunction has been implicated in neuropsychiatric diseases, such as schizophrenia and anxiety disorders, primarily characteri...

Previous studies have demonstrated activation of dopamine transmission in the medial prefrontal cortex (mPFC) by conditioned fear stimuli. Therefore, the present study investigated the functional significance of mPFC dopamine for a conditioned fear response to a tone. We examined the effects of inhibition or stimulation of mPFC dopamine transmissio...

Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning...

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Ac...

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating and is decreased in neuropsychiatric diseases, including schizophrenia. Hippocampal involvement in PPI has been the subject of several studies, in particular, as aberrant hippocampal activity has been associated with schizophrenia. In rats, chemical stimu...

Dopamine (DA) in mammalian associative structures, such as the prefrontal cortex (PFC), plays a prominent role in learning and memory processes, and its homeostasis differs from that of DA in the striatum, a sensorimotor region. The neostriatum caudolaterale (NCL) of birds resembles the mammalian PFC according to connectional, electrophysiological,...

Prepulse inhibition (PPI) of the acoustic startle response and open-field locomotor activity were measured after bilateral infusion of N-methyl-D-aspartate into the ventral (0.10, 0.25, 0.50 microg/side) and dorsal (0.10, 0.25, 0.50, 0.70 microg/side) hippocampus of Wistar rats. Dose-dependent hyperactivity and disruption of PPI--behavioral effects...

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fe...

Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hyperactivity...

Studies on the involvement of the rat hippocampus in classical fear conditioning have focused mainly on the dorsal hippocampus and conditioning to a context. However, the ventral hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consis...

Studies on the involvement of the rat hippocampus in classical fear conditioning have focused mainly on the dorsal hippocampus and conditioning to a context. However, the ventral hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consis...

Rationale: Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hy...

This study re-examined the hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the rat ventral hippocampus and compared how both effects were affected by pretreatment with either haloperidol or clozapine. While the hyperactivity is thought to depend on dopamine receptor activation in the nucleus accumb...

Disruption of prepulse inhibition (PPI) induced by NMDA receptor antagonists, such as MK801, has been used as an animal model of positive and negative symptoms of schizophrenia. Previous studies suggested that atypical, but not typical, neuroleptics can selectively restore MK801-induced PPI disruption and that such selectivity may depend on strain...

Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient i...