Memory consolidation and sleep
Lead Research Organisation:
University of Cambridge
Department Name: Zoology
Abstract
The project will elucidate molecular mechanisms of memory, of sleep and of the relationship between them by studying the intermediate and medial mesopallium (IMM), a forebrain region of the domestic chick strongly implicated in the learning process of imprinting. The available evidence strongly indicates that the IMM is a region in which information about the imprinting stimulus is stored as a result of learning. Recent research supported by the BBSRC has shown that sleep during a period shortly after training is required for stabilization of neuronal responsiveness in the IMM to an imprinting stimulus, and also for consolidation of memory for the imprinting stimulus. The project will determine which phases of sleep are important for the memory consolidation and enquire whether mild, non-invasive electrical stimulation of the brain can reverse the effects of sleep disruption on memory and neuronal tuning in the IMM to the imprinting stimulus. The project seeks to extend our understanding of memory mechanisms and in consequence may provide a rational basis for potential treatments of memory disorders. Memory and sleep are of paramount importance to human life, and research at both the behavioural and the neurobiological level is essential if these phenomena are to be understood satisfactorily. This understanding is particularly important if the many clinical neurological disorders that involve memory impairment are to be treated effectively. It is sometimes desirable to enhance memory and at other times to reduce it, as in the case of persistent aversive memories that may be associated with certain psychiatric disorders. A possible outcome of this work is the identification of sleep phases, the modification of which may therapeutically enhance or reduce memory, and a sound understanding of the neurobiological basis of such therapies.
Technical Summary
The proposal investigates molecular mechanisms of memory, sleep and the relationship between them by studying the IMM, a forebrain region of the domestic chick strongly implicated in the learning process of imprinting. The evidence indicates that information about the imprinting stimulus (IS) is stored in the IMM. Sleep shortly after training is required for stabilization of neuronal responsiveness in the IMM to an IS, and for consolidation of memory of the IS. The objectives are: 1. Measurement of the effects of reduction of paradoxical sleep, slow wave sleep and sleep rich in 5-6 Hz EEG activity, on memory (retention of a preference acquired through imprinting). Specific phases of sleep will be disturbed during the six-hour period shortly after training (Session 1), when memory consolidation is vulnerable to random sleep disturbance. As a control, the specific disturbance will be applied during a later six-hour period (Session 2), when consolidation has been found to be insensitive to random sleep disturbance. 2. Selection of the specific sleep disturbance protocol that is most effective on memory consolidation (see Objective 1). Measurement of the effect of this protocol on neuronal responsiveness to the IS in the IMM following imprinting training. 3. Disturbance of sleep (thus disrupting long-term memory) by arousing chicks at random times during Session 1. In these chicks, determination of the effect on IMM neuronal responsiveness to the IS, and on memory, of slow (0.75 Hz) and theta (5-6 Hz) transcranial stimulation during Session 1. Sleep will be monitored using EEG from skull electrodes, nuchal EMG and video monitoring. Bilaterally implanted tetrodes in the IMM will be used for neuronal recording, followed by off-line spike sorting. The EEG will be subjected to real-time frequency analysis and used with rectified EMG to identify sleep phases. Sleep will be disrupted automatically by the interface monitoring the electrophysiological signals.
Planned Impact
Potential beneficiaries of the research (i) Those who would benefit from learning more about memory mechanisms. The neuroscience research community; school students; academic colleagues who are not science specialists; commercial organisations; the Home Office (Animals (Scientific Procedures) Act section and others); health professionals; the wider public who may be informed of the research via the media. (ii) Those who would benefit from the application of the results of the research (indirectly because the research employs an animal model of human memory). Patients suffering from certain neurological and psychiatric disorders; human subjects, such as night-shift workers, who are subject to occupational modification of their sleep patterns; medical professionals; those involved in the production of medical and neurophysiological equipment. Communication of the research Results will be communicated normally via the scientific literature. In addition, seminars in schools and talks to lay audiences will be organised each year in continuation of current practice. Relevant results will be communicated to the Home Office Inspectorate and existing links with radio, television, the Civil Service, Government and commercial organisations will be employed as in the past to communicate the results to as wide an audience as possible. Current development of equipment and software in our laboratory will be exploited commercially or made available to user communities as appropriate. All communications activities will rely on assistance from the University of Cambridge Office of External Affairs and Communications (OEC). The University Computing Service will advise on publicity website design, which will be effected by the RA, the technician, the PI and the Computer Officer whose time is costed in the resources requested. Any medical benefits flowing from the research are likely to be realised after publication in the usual way. However, information flow will be facilitated by publicising findings via the Cambridge Neuroscience website, which communicates significant new findings to a wide, multidisciplinary community within and outside the University of Cambridge. Attendance at meetings of the Society for Neuroscience can be particularly effective for establishing scientific and commercial links. Funds have therefore been requested to allow the PI and the RA to attend two successive annual meetings of the Society. Exploitation and Application Commercially exploitable findings will be handled by Cambridge Enterprise, an organisation associated with the University of Cambridge and available for this purpose. Exploitable findings might include the identification of a particular sleep phase which is closely associated with memory consolidation and a brain stimulation regime which is particularly effective on consolidation. Results will be monitored continuously to identify exploitable findings. Cambridge Enterprise will advise as necessary on protection of such findings at the end of the project. Capability Outreach activities will be conducted by the PI, the RA and Professor Sir Gabriel Horn, who will collaborate in all phases of the project. Professor Horn and I have substantial experience of describing our work to the general public but we will, as in the past, rely on the OEAC and the Press Officer in the Department of Zoology for advice. Communication training for the RA will be organised as appropriate, with the assistance of OEAC and courses offered by the University Human Resources team. Resource for the activity The resources needed for Impact activities are a component of the salary of a Computer Officer and the sum requested for Travel.
People |
ORCID iD |
Brian McCabe (Principal Investigator) |
Publications
Margvelani G
(2018)
Mitochondrial fusion and fission proteins and the recognition memory of imprinting in domestic chicks.
in Neuroreport
McCabe B
(2017)
Lateralized Brain Functions
McCabe BJ
(2013)
Imprinting.
in Wiley interdisciplinary reviews. Cognitive science
Meparishvili M
(2015)
A Proteomic Study of Memory After Imprinting in the Domestic Chick.
in Frontiers in behavioral neuroscience
Moorman S
(2015)
Memory-related brain lateralisation in birds and humans.
in Neuroscience and biobehavioral reviews
Nicol AU
(2014)
Olfactory bulb encoding during learning under anesthesia.
in Frontiers in behavioral neuroscience
Nicol AU
(2015)
Complex spike patterns in olfactory bulb neuronal networks.
in Journal of neuroscience methods
Nicol, A. U.
(2014)
Transcranial stimulation promotes consolidation of imprinted memory in domestic chicks (Gallus gallus)
in Proc Physiol Soc
Nicol, A. U.
(2012)
Sleep, theta activity and memory consolidation
in Neuroscience 2012
Description | 1. Electrophysiological consequences of imprinting The IMM is a region is a memory system in the chick forebrain for the learning process of imprinting. It has been found (i) that neurons in the IMM respond specifically to individual animals used as imprinting stimuli; (ii) that IMM neurons respond more strongly to visual or auditory components of a compound audiovisual imprinting stimulus than to the compound stimulus itself; (iii) that there is a progressively increasing functional association between the IMM and the hippocampus, a region implicated in spatial learning, in a period shortly after learning during which sleep-dependent memory consolidation has been found to occur. 2. Theta-compensation in the electroencephalogram (EEG) and memory impairment by disruption of slow-wave sleep Chicks were trained with an imprinting stimulus and shortly afterwards, in the post-training period known to be critical for memory for the imprinting stimulus, they were awakened when theta waves (4-8 cycles/s) appeared in the EEG during sleep. This was to determine whether deprivation of theta-rich sleep impaired memory recall in the same way as random awakening has previously been shown to do. It was not possible to reduce the total amount of theta activity: i.e. more theta was generated in compensation, and memory was not impaired. The chick may thus contribute to the understanding of the mechanisms of an effect previously reported in human subjects. It was possible to reduce the amount of slow-wave sleep (0.75 cycles/s in the EEG) in the critical post-training period after imprinting and this procedure impaired memory for the imprinting stimulus to approximately the same extent as random awakening. The effect of the latter could thus be accounted for by an effect on slow-wave sleep. 3. Protection of sleep-dependent memory impairment by electrical stimulation In a further experiment, chicks' sleep was disturbed at random during the critical post-training period after imprinting. This produced memory impairment, replicating results of a previous study. Chicks treated thus, but which in addition received transcranial electrical stimulation at either 0.75 cycles/s (i.e. the frequency predominant in slow-wave sleep) or theta frequency did not show this impairment. Thus, electrical stimulation at the frequencies implicated in memory consolidation by previous experiments, were protective against memory impairment due to sleep disturbance. 4. A contribution to the development and validation of a new method for the identification of temporal patterns in neuronal spike trains. |
Exploitation Route | By acting as a springboard for further research into memory mechanisms. The neural processes by which sleep modifies memory are poorly understood and yet such understanding is necessary for the maintenance of mental health and the treatment of cognitive disorders. Our results have contributed to progress in these fields. |
Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
Title | Spike processing methodology |
Description | Publication of novel electrophysiological analysis methodology by Dr AU Nicol. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Increased efficiency of electrophysiological spike processing. |
URL | http://www.sciencedirect.com/science/article/pii/S0165027014003410 |
Description | Mechanisms of filial imprinting in the domestic chick |
Organisation | Ilia State University |
Country | Georgia |
Sector | Academic/University |
PI Contribution | Behavioural training and testing; electrophysiological and statistical expertise. |
Collaborator Contribution | Biochemical analysis. |
Impact | Publications with R. O. Solomonia listed under Publication. DOIs: 10.1016/j.neubiorev.2014.09.013 10.1007/s00221-013-3435-2 10.3389/fnbeh.2015.00319 10.1016/j.neuroscience.2011.07.053 10.1007/s00221-008-1428-3 10.1113/j.physiol.2005.098012 10.1046/j.1460-9568.2003.02539.x 10.1097/00001756-200009280-00020 10.1046/j.1460-9568.1998.00354.x 10.1037/0735-7044.112.3.646 10.1016/S0306-4522(97)00123-1 All publications are the result of multidisciplinary collaboration. See above entries for the disciplines involved. |
Description | The effect of sleep on memory consolidation |
Organisation | Saitama Medical University |
Country | Japan |
Sector | Academic/University |
PI Contribution | Behavioural training facilities; electrophysiological expertise; statistical analysis. |
Collaborator Contribution | Histochemical expertise; design of behavioural experiments; image analysis; consumables. Contribution of data from immediate-early gene expression in chick brain complementing electrophysiological data. |
Impact | Neuroscience 2013 abstract: 'Sleep and Fos-like immunoreactivity in a chick forebrain memory region after filial imprinting' (see publications). |
Start Year | 2011 |
Description | Neuroscience masterlass |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Interactive workshop on neuroscience to school sixth-form students. |
Year(s) Of Engagement Activity | 2017 |
Description | Research talk to non-specialist academic staff and students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Talk generated questions and discussions. References and a further talk were requested. |
Year(s) Of Engagement Activity | 2006,2011 |
Description | Research talk to non-specialists |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Description of my research supported by BBSRC. |
Year(s) Of Engagement Activity | 2017 |
Description | Sermon on science and religion |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Discussion and requests for references afterwards. Stimulated further talks by colleagues. |
Year(s) Of Engagement Activity | 2013 |
URL | https://www.robinson.cam.ac.uk/chapel/sermons/science-and-religion/science-and-religion-sermon-2 |
Description | Workshop for heads of sixth form |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Very positive feedback. Active discussion and participation in experiments and seminars. Requests for further technical information about the experiments demonstrated. |
Year(s) Of Engagement Activity | 2013 |
Description | Workshop for prospective undergraduates |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Demonstrations of electrophysiological experiments stimulated enthusiastic discussion. Very positive feedback; workshop was cited as a reason for choosing a particular course. |
Year(s) Of Engagement Activity | 2013 |