September 22nd – Antonis Asiminas (University of Edinburgh)
SM4, Maths
Sustained correction of associative learning deficits following brief, early treatment in a rat model of Fragile X Syndrome.’ Fragile X Syndrome (FXS) is a major heritable cause of intellectual disability and autism. Despite the early emergence of symptoms associated with FXS, it is still not clear whether treatments restricted to early development of brain circuits can permanently prevent impairments in cognitive function. In the work I’ll present, we examine the developmental trajectory of learning and memory in a rat model of FXS using spontaneous object exploration tasks and tested whether temporary early intervention can prevent the emergence of cognitive deficits later in life.
http://www.ccns.ed.ac.uk/People/Postdocs/asiminas.html
September 29th – Ole Jensen (University of Birmingham)
SM3, Maths
Hunting For Phase Coding
In 1993 O’Keefe and Recce demonstrated that hippocampal place cells fire in phase specific manner with respect to ongoing theta oscillations. This suggests that slower oscillations serve to organize a code in which individual objects are activated as a sequence within a cycle. I will discuss the functional consequences of this phenomenon and to what extend the principle generalized to other rhythms such as human alpha oscillations.
Suggested readings:
Jensen, O., Gips, B., Bergmann, T.O. and Bonnefond, M. (2014) Temporal coding organized by coupled alpha and gamma oscillations prioritize visual processing. Trends in Neurosciences
Lisman, J.E. and Jensen, O. (2013) The theta-gamma neural code. Neuron 77:1002-1016
http://www.birmingham.ac.uk/schools/psychology/people/profile.aspx?ReferenceId=125382
October 20th – Lisa Genzel (Donders Institute)
Sleep for systems consolidation
Distinct forms of memory consolidation (cellular and systems) influence the persistence of spatial memory within the hippocampus (cellular) and following hippocampal-neocortical interactions (systems). Factors influencing these processes include: (1) novelty exposure that enhances the persistence of hippocampal traces via neuromodulation; and (2) sleep that aids systems consolidation and thus cortical memory. In a sequence of experiments, we could show that sleep leads to systems consolidation via learning-dependent cortical consolidation. In contrast, novelty tags a memory to remain more hippocampal by increasing gene expression. Further, I will show evidence that different behaviour such as novelty and normal learning influence hippocampal-cortical communication during subsequent sleep and such behaviours after learning influence the behavioural expression of memory.
http://www.ru.nl/excellence/laureates-0/current-members-0/current-members/dr-lisa-genzel/
October 27th – Pooran Dewari (University of Edinburgh)
LT1, 43 Woodland Road
An efficient and scalable CRISPR/Cas9 pipeline for epitope tagging in mammalian stem cells
CRISPR-Cas9 technology has revolutionized genome editing at an unprecedented scale across multiple organisms and cell types. Knock-in of small epitope tags into endogenous genes simplifies antibody-based assays, overcoming issues of specificity and sensitivity. We have developed a highly efficient and scalable Cas9 ribonucleoprotein(RNP)-assisted method for epitope tagging in mouse and human primary neural stem (NS) cells and glioblastoma tumour-derived cultures. Delivery of RNP complexes containing synthetic dual-guide RNA (crRNA 36-mer and tracrRNAs 67-mer) facilitates efficient knock-in of V5 tag (5-30%) in mouse NS cells without requirements for any selection strategy. Similar efficiencies were achieved in human NS and glioma stem cells. Importantly, with these optimized conditions and a newly developed web-based tool for crRNA and donor DNA design, we were able to demonstrate medium-throughput epitope tagging in a 96-well plate format. 192 transcription factors (key regulators of neural stem cell self-renewal and differentiation) were tested for tagging in parallel, and 60 of these were effectively tagged with V5. Our method provides a step-change in our ability to interrogate mammalian proteins in stem cells and their glioma counterparts. As a proof-of –principle, we used the newly tagged Sox2-V5 glioma cell lines and performed ChIP-SICAP (selective isolation of chromatin associated proteins) to identify on-chromatin partners of Sox2 transcription factor. In summary, we have developed a highly efficient and scalable pipeline for tagging of endogenous proteins in mouse and human neural and glioma stem cells using off-the-shelf reagents. Our method will enable elucidation of the subcellular localisation and interaction partners for a multitude of mouse and human proteins.
http://www.crm.ed.ac.uk/people/pooran-dewari
November 3rd – James Rankin (University of Exeter)
Dynamics of visual and auditory perception
Ambiguous sensory stimuli provide a unique opportunity to characterize intrinsic neural dynamics of cortical processing. The perceptual interpretation of fixed sensory stimuli can switch spontaneously due to ambiguity, so-called perceptual bistability. Common examples discussed here include binocular rivalry, ambiguous motion and the auditory streaming paradigm. Dynamical systems modelling has helped to reveal the common computational mechanisms behind perceptual bistability. A canonical model that incorporates three competition mechanisms (mutual inhibition, slow adaptation and noise) is adapated to investigate processing across the different sensory modalities. The work helps to reveal the mechanisms behind attention, the role of contrast for visual stimuli and how sudden stimulus changes can drive perceptual switching.
http://emps.exeter.ac.uk/mathematics/staff/jar226
November 10th – Nicholas Robinson (UCL)
LT1, 43 Woodland Road
Hippocampal-Medial Entorhinal Interactions Underlying Memory Encoding and the All-Optical Interrogation of Hippocampal Function
The talk will initially cover work looking at the importance of medial entorhinal cortex activity for the expression of hippocampal neural correlates during epochs of spatial, temporal and object based experience, and the importance of this coding for on going memory performance. The study utilized large scale optogenetic inactivation while simultaneously performing tetrode recordings in animals performing an object-delay-response association task. It will then move onto current work using ‘all-optical physiology’, the 2-photon calcium imaging of the activity of a large population of neurons while using a second light path to provide cellular resolution optogenetic control of a chosen subset of the same population. This allows the manipulation of a functionally defined population of neurons rather than relying on genetic targeting. The technique is being applied to determine the link between specific place field firing, memory and behaviour.
https://iris.ucl.ac.uk/iris/browse/profile?upi=ROBIN13
November 17th – Stuart Allan (University of Manchester)
AIMS 2A/B
Inflammation and stroke: contributions across the whole patient journey, from risk to recovery
Stroke is a leading cause of death and disability yet there are few effective therapeutic interventions. It is now well recognised that inflammation is a key aspect of the different risk factors for stroke and also contributes to the acute injury. In addition inflammation likely plays an important role in the resolution of ischaemic injury and in the repair and recovery processes in the damaged brain. The pro-inflammatory cytokine interleukin-1 is a key mediator of sterile inflammation and there is a substantial body of evidence to suggest it may be an effective therapeutic target. In this seminar these different aspects of the role of inflammation in stroke will be discussed.
https://www.research.manchester.ac.uk/portal/stuart.allan.html
November 24th – Michael Kohl (University of Oxford)
LT1, 43 Woodland Road
Roles of hippocampus, retrosplenial cortex, and neocortex in learning and memory in mice – from synapse to behaviour
We identified a left-right dissociation of synaptic plasticity in the mouse hippocampus. To investigate possible effects on behaviour, we used optogenetics to unilaterally silence hippocampal CA3 pyramidal cells in mice performing hippocampus-dependent memory tasks. Whilst silencing of either the left or the right CA3 caused a short-term memory deficit, strikingly, only left CA3 silencing impaired long-term memory. Our data suggests that memory is routed via distinct left-right pathways within the mouse hippocampus. We are currently investigating whether this hemispheric specialisation extends to neocortical structures involved in associative memory. Recent data implicates the retrosplenial cortex in sensory preconditioning, a form of associative learning, and suggests that retrosplenial cortex aids learning in the neocortex by providing top-down inputs to primary sensory cortex.
https://www.neuroscience.ox.ac.uk/research-directory/michael-kohl
December 8th – Andrew Jarman (University of Edinburgh)
LT1, 43 Woodland Road
Mechanotransduction mechanisms in Drosophila mechanosensory neurons
We are interested in both the development and the physiology of mechanosensory neurons, primarily in Drosophila. In this presentation I will concentrate on physiology. I will initially talk about our attempts to define the mechanotransduction process in poorly studied larval stretch receptors that resemble mammalian muscle spindles. This will include some basic modelling, as well as electrophysiology and optogenetics. As time allows, I will also discuss a different class of mechanosensory neuron, required for hearing and proprioception. These neurons appear to generate active movements in response to sound (analogous to the movements of our inner ear hair cells that form the ‘cochlear amplifier’). I will discuss the possible molecular basis of this process.
https://www.ed.ac.uk/integrative-physiology/staff-profiles/research-groups/andrew-jarman
December 15th – Jess Gaunt (University of Bristol)
LT1, 43 Woodland Road
Exploring changes in the CA1 translatome during associative recognition memory formation
Gene expression is required for long term changes at the synapse underlying memory formation. Messenger RNAs undergoing translation into protein in specific cell types can be profiled using Translating Ribosome Affinity Purification (TRAP; Heiman et al, 2008; Doyle et al, 2008). Profiling the translatome instead of the transcriptome (as in standard RNAseq experiments) enables protein abundance to be estimated more accurately, has greater temporal specificity, and is sensitive to changes in both transcription and translation.
To investigate genome-wide gene expression in rats during associative recognition memory formation, a novel TRAP virus was targeted to neurons in CA1 of the hippocampus using intracerebral injections and combined with Next Generation Sequencing (NGS) andPaired Viewing (PV), a within-subjects paradigm to induce differential gene expression in CA1 when novel and familiar configurations of stimuli are presented (Wan et al, 1999). Leveraging recent developments in bioinformatics, changes in the translatome in the hours following PV were investigated. This talk will discuss making reliable inferences from multi-factor NGS data and interesting features of this complex dataset.