Seminars

Prosopometamorphopsia (PMO) is a disorder characterized by face perception distortions. People with PMO see facial features that appear to melt, stretch, and change size and position. I'll discuss research on PMO carried out by my lab and others that sheds light on the cognitive and neural organization of face perception. https://facedistortion.faceblind.org/

Dictyostelium Discoideum (DD) are a fascinating single-cellular organism. When nutrients are plentiful, the DD cells act as autonomous individuals foraging their local vicinity. At the onset of starvation, a few (<0.1%) cells begin communicating with others by emitting a spike in the chemoattractant protein cyclic-AMP. Nearby cells sense the chemical gradient and respond by moving toward it and emitting a cyclic-AMP spike of their own. Cyclic-AMP activity increases over time, and eventually a spiral wave emerges, attracting hundreds of thousands of cells to an aggregation center. How DD cells go from autonomous individuals to a collective entity remains an open question for more than 60 years--a question whose answer would shed light on the emergence of multi-cellular life. Recently, trans-scale imaging has allowed the ability to sense the cyclic-AMP activity at both cell and colony levels. Using both the images as well as toy simulation models, this research aims to clarify whether the activity at the colony level is in fact initiated by a few cells, which may be deemed "leader" or "pacemaker" cells. In this talk, I will demonstrate the use of information-theoretic techniques to classify leaders and followers based on trajectory data, as well as to infer the domain of interaction of leader cells. We validate the techniques on toy models where leaders and followers are known, and then try to answer the question in real data--do leader cells drive collective behavior in DD colonies?

At any given moment the brain receives more sensory information than it can use to guide adaptive behaviour, creating the need for mechanisms that promote efficient processing of incoming sensory signals. One way in which the brain might reduce its sensory processing load is to encode successive presentations of the same stimulus in a more efficient form, a process known as neural adaptation. Conversely, when a stimulus violates an expected pattern, it should evoke an enhanced neural response. Such a scheme for sensory encoding has been formalised in predictive coding theories, which propose that recent experience establishes expectations in the brain that generate prediction errors when violated. In this webinar, Professor Jason Mattingley will discuss whether the encoding of elementary visual features is modulated when otherwise identical stimuli are expected or unexpected based upon the history of stimulus presentation. In humans, EEG was employed to measure neural activity evoked by gratings of different orientations, and multivariate forward modelling was used to determine how orientation selectivity is affected for expected versus unexpected stimuli. In mice, two-photon calcium imaging was used to quantify orientation tuning of individual neurons in the primary visual cortex to expected and unexpected gratings. Results revealed enhanced orientation tuning to unexpected visual stimuli, both at the level of whole-brain responses and for individual visual cortex neurons. Professor Mattingley will discuss the implications of these findings for predictive coding theories of sensory encoding. Professor Jason Mattingley is a Laureate Fellow and Foundation Chair in Cognitive Neuroscience at The University of Queensland. His research is directed toward understanding the brain processes that support perception, selective attention and decision-making, in health and disease.

This seminar will focus on the extraordinary shift in migraine research during the last 4 decades with the discovery of the trigeminovascular system (TVS) and it’s major impact on pathophysiology and treatment. Compelling evidence supporting the importance of TVS, cortical spreading depression and parameningeal inflammation will be explored as will the implications of newly discovered microvascular channels within the meninges on an attack.

The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that repeated cholinergic activation of 𝛼7 nACh receptors expressed in oriens-lacunosum-moleculare (OLM𝛼2) interneurons could induce LTP in SC-CA1 synapses. We used a biophysically realistic computational model to examine mechanistically how cholinergic activation of OLMa2 interneurons increases SC to CA1 transmission. Our results suggest that, when properly timed, activation of OLMa2 interneurons cancels the feedforward inhibition onto CA1 pyramidal cells by inhibiting fast-spiking interneurons that synapse on the same dendritic compartment as the SC, i.e., by disinhibiting the pyramidal cell dendritic compartment. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of synaptic plasticity. We found that locally-reduced GABA release (disinhibition) paired with SC stimulation could lead to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the excitatory synapse. Our work suggests that inhibitory synapses critically modulate excitatory neurotransmission and induction of plasticity at excitatory synapses. Our work also shows how cholinergic action on OLM interneurons, a mechanism whose disruption is associated with memory impairment, can down-regulate the GABAergic signaling into CA1 pyramidal cells and facilitate potentiation of the SC-CA1 synapse.

CA3-CA1 synapses in the hippocampus are the initial locus of episodic memory. The action of acetylcholine alters cellular excitability, modifies neuronal networks, and triggers secondary signaling that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model to describe the activation of postsynaptic M1 receptors that leads to IP3 production from membrane PIP2 molecules. The binding of IP3 to IP3 receptors in the endoplasmic reticulum (ER) ultimately causes calcium release. This calcium release from the ER activates potassium channels like the calcium-activated SK channels and alters different aspects of synaptic signaling. In an independent signaling cascade, M1 receptors also directly suppress SK channels and the voltage-activated KCNQ2/3 channels, enhancing post-synaptic excitability. In the CA3 presynaptic terminal, we model the reduction of the voltage sensitivity of voltage-gated calcium channels (VGCCs) and the resulting suppression of neurotransmitter release by the action of the M4 receptors. Our results show that the reduced initial release probability because of acetylcholine alters short-term plasticity (STP) dynamics. We characterize the dichotomy of suppressing neurotransmitter release from CA3 neurons and the enhanced excitability of the postsynaptic CA1 spine. Mechanisms underlying STP operate over a few seconds, while those responsible for LTP last for hours, and both forms of plasticity have been linked with very distinct functions in the brain. We show that the concurrent suppression of neurotransmitter release and increased sensitivity conserves neurotransmitter vesicles and enhances the reliability in plasticity. Our work establishes a relationship between STP and LTP coordinated by neuromodulation with acetylcholine.

Many animals are highly visual. They view their world through photoreceptors sensitive to different wavelengths of light. Animal survival and optimal behavioral performance may select for varying photoreceptor sensitivities depending on animal habitat or visual tasks. Our goal is to understand what drives visual diversity from both an evolutionary and molecular perspective. The group of more than 2000 cichlid fish species are an ideal system for examining such diversity. Cichlid are a colorful group of fresh water fishes. They have undergone adaptive radiation throughout Africa and the new world and occur in rivers and lakes that vary in water clarity. They are also behaviorally complex, having diverse behaviors for foraging, mate choice and even parental care. As a result, cichlids have highly diverse visual systems with cone sensitivities shifting by 30-90 nm between species. Although this group has seven cone opsin genes, individual species differ in which subset of the cone opsins they express. Some species show developmental shifts in opsin expression, switching from shorter to longer wavelength opsins through ontogeny. Other species modify that developmental program to express just one of the sets, causing the large sensitivity differences. Cichlids are therefore natural mutants for opsin expression. We have used cichlid diversity to explore the relationship between visual sensitivities and ecology. We have also exploited the genomic power of the cichlid system to identify genes and mutations that cause opsin expression shifts. Ultimately, our goal is to learn how different cichlid species see the world and whether differences matter. Behavioral experiments suggest they do indeed use color vision to survive and thrive. Cichlids therefore are a unique model for exploring how visual systems evolve in a changing world.

While time-averaged dynamics of brain functional connectivity are known to reflect the underlying structural connections, the exact relationship between large-scale function and structure remains an unsolved issue in network neuroscience. Large-scale networks are traditionally observed by correlation of fMRI timecourses, and connectivity of source-reconstructed electrophysiological measures are less prominent. Accessing the brain by using multimodal recordings combining EEG, fMRI and diffusion MRI (dMRI) can help to refine the understanding of the spatio-temporal organization of both static and dynamic brain connectivity. In this talk I will discuss our prior findings that whole-brain connectivity derived from source-reconstructed resting-state (rs) EEG is both linked to the rs-fMRI and dMRI connectome. The EEG connectome provides complimentary information to link function to structure as compared to an fMRI-only perspective. I will present an approach extending the multimodal data integration of concurrent rs-EEG-fMRI to the temporal domain by combining dynamic functional connectivity of both modalities to better understand the neural basis of functional connectivity dynamics. The close relationship between time-varying changes in EEG and fMRI whole-brain connectivity patterns provide evidence for spontaneous reconfigurations of the brain’s functional processing architecture. Finally, I will talk about data quality of connectivity derived from concurrent EEG-fMRI recordings and how the presented multimodal framework could be applied to better understand focal epilepsy. In summary this talk will give an overview of how to integrate large-scale EEG networks with MRI-derived brain structure and function. In conclusion EEG-based connectivity measures not only are closely linked to MRI-based measures of brain structure and function over different time-scales, but also provides complimentary information on the function of underlying brain organization.

Although analogical reasoning has been assumed to involve insight and its associated “aha!” experience, the relationship between these phenomena has never been directly probed empirically. In this study we investigated the relationship between representational change and the “aha!” experience during analogical reasoning. A novel set of verbal analogy stimuli were developed for use as an insight task. Across two experiments, participants reported significantly stronger aha moments and showed greater evidence of representational change on trials with more semantically distant analogies. Further, the strength of reported aha moments was correlated with the degree to which participants’ descriptions of the analogies changed over the course of each trial. Lastly, we probed the individual differences associated with a tendency to report stronger "aha" experiences, particularly related to mood, curiosity, and reward responsiveness. The findings shed light on the affective components of analogical reasoning and suggest that measuring affective responses during such tasks may elucidate novel insights into the mechanisms of creative analogical reasoning.

Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an increasingly utilized approach for neurological disease modeling with patient-derived cells. Several groups, including ours, have applied the iPSC approach to model severe genetic developmental and epileptic encephalopathies (DEEs) with patient-derived cells. Although most studies to date involve 2-D cultures of patient-derived neurons, brain organoids are increasingly being employed to explore genetic DEE mechanisms. We are applying this approach to understand PMSE (Polyhydramnios, Megalencephaly and Symptomatic Epilepsy) syndrome, Rett Syndrome (in collaboration with Ben Novitch at UCLA) and Protocadherin-19 Clustering Epilepsy (PCE). I will describe our findings of robust structural phenotypes in PMSE and PCE patient-derived brain organoid models, as well as functional abnormalities identified in fusion organoid models of Rett syndrome. In addition to showing epilepsy-relevant phenotypes, both 2D and brain organoid cultures offer platforms to identify novel therapies. We will also discuss challenges and recent advances in the brain organoid field, including a new single rosette brain organoid model that we have developed. The field is advancing rapidly and our findings suggest that brain organoid approaches offers great promise for modeling genetic neurodevelopmental epilepsies and identifying precision therapies.

We have characterised the motility of the swimming microalga Chlamydomonas reinhardtii as a function of day/night cycles, to which the microalgal growth is entrained. Intriguingly, we find that the microalgae swim almost twice as fast during the night than during the day. I will connect this result with the bioenergetics of flagellar propulsion, discussing consequences for the distributions of cells in lab-based and environmental water columns.