Balanced neural activity within hippocampal-prefrontal circuit and cognitive flexibility.
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Psychology
Abstract
Area: Behavioural neuroscience
Methods (Preclinical): Cognitive and behavioural testing of cognitive flexibility, intra-cerebral drug micro-infusions, electrophysiology, anatomical tract-tracing and histology.
Animal Model: Rats
Healthy brain activity requires a balance of excitatory and inhibitory neurotransmission (Isaacson and Scanziani, 2011, Neuron) . Activity imbalances, caused by reductions in inhibitory GABA transmission (producing "disinhibition") in brain regions mediating cognitive function, such as the hippocampus and prefrontal cortex, have been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline (Marin, 2012, Nature Rev Neurosci; Huang & Mucke, 2012, Cell). However, the role of balanced cortico-hippocampal activity in distinct cognitive functions has yet to be clarified.
Recent pharmacological studies manipulating the activity balance of the rat prefrontal cortex or hippocampus have found that, not only do imbalanced neural activity levels in hippocampus and prefrontal cortex impair the respective region-dependent memory and attention functions, but hippocampal disinhibition disrupts prefrontal-dependent attention (Pezze et al, 2014, J Neurosci; McGarrity et al, 2016, Cerebral Cortex). Based on these findings, using recently-developed operant cognitive flexibility tasks combined with GABA-ergic manipulation, we will examine if balanced cortico-hippocampal activity is similarly required for another prefrontal-dependent function, cognitive flexibility. Cognitive flexibility allows adaptation of behavioural responses to suit changing environmental demands, is sensitive to prefrontal GABA-ergic perturbations, and is consistently defective in schizophrenia patients.
Methods (Preclinical): Cognitive and behavioural testing of cognitive flexibility, intra-cerebral drug micro-infusions, electrophysiology, anatomical tract-tracing and histology.
Animal Model: Rats
Healthy brain activity requires a balance of excitatory and inhibitory neurotransmission (Isaacson and Scanziani, 2011, Neuron) . Activity imbalances, caused by reductions in inhibitory GABA transmission (producing "disinhibition") in brain regions mediating cognitive function, such as the hippocampus and prefrontal cortex, have been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline (Marin, 2012, Nature Rev Neurosci; Huang & Mucke, 2012, Cell). However, the role of balanced cortico-hippocampal activity in distinct cognitive functions has yet to be clarified.
Recent pharmacological studies manipulating the activity balance of the rat prefrontal cortex or hippocampus have found that, not only do imbalanced neural activity levels in hippocampus and prefrontal cortex impair the respective region-dependent memory and attention functions, but hippocampal disinhibition disrupts prefrontal-dependent attention (Pezze et al, 2014, J Neurosci; McGarrity et al, 2016, Cerebral Cortex). Based on these findings, using recently-developed operant cognitive flexibility tasks combined with GABA-ergic manipulation, we will examine if balanced cortico-hippocampal activity is similarly required for another prefrontal-dependent function, cognitive flexibility. Cognitive flexibility allows adaptation of behavioural responses to suit changing environmental demands, is sensitive to prefrontal GABA-ergic perturbations, and is consistently defective in schizophrenia patients.
Organisations
People |
ORCID iD |
| Tobias Bast (Primary Supervisor) | |
| Jeremy Roberts (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 01/10/2015 | 31/10/2024 | |||
| 1644954 | Studentship | BB/M008770/1 | 01/10/2015 | 30/09/2019 |
| Description | Healthy Brains at Every Age - Public invited to university to take part in human anaolgues of rodent spatial memory tasks |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Healthy Brains was an event by the Psychology department in collaboration with Cambridge cognition, for members of the public, attended primarily by elderly and young people/adolescents. The aim was to present the public with information about how we study cognition and brain mechanisms thereof, and how aging may affect brain and behaviour. Our activity was the computer-based "virtual water-maze" task in which participants could test their spatial navigation memory. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Presentation of activity at Pint of Science, Nottingham 2019 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | The activity was an interactive game for participants to learn about research conducted within our group which studied effects of inhibiting neural pathways on rapid place learning as tested in the water maze (WM) delayed matching to place task (DMTP). Participants also viewed videos compilations demonstrating a rat water maze experiment. This was done to support a talk about research into the neural substrates of cognition presented by Dr Bast to the audience attending this Pint of Science event. This led to audience members, mainly members of the general public, asking questions and being involved in disscussion. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Wonder 2017 - University of Nottingham |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | For Wonder 2017, a day-long public science fair, we hosted the computer-based "virtual water-maze" task in which participants could test their spatial navigation memory. This was presented in collaboration with the Arthritis Research UK Pain Centre, with the premise that chronic pain may induce neurological changes in the brain, resulting in memory impairments. On this day, we also presented a video compilation I made of the rat water maze lab experiment. |
| Year(s) Of Engagement Activity | 2017 |