Fellows Lecture in Pairs: “Descending Cortical Loops for Auditory Plasticity” and “Form and function in the developing heart”

Associate Professor Victoria Bajo Lorenzana: “Descending Cortical Loops for Auditory Plasticity”

The ability to modify the neural activity evoked by sensory experience is the basis of learning. Descending projections from cortical areas are among the most prominent pathways in any sensory system, suggesting their role in modulating subcortical processing. In this seminar, I will provide details and examples about how corticofugal connections contribute to auditory perception and multisensory integration.
One of the main neural loops connects the primary auditory areas with the core auditory thalamus. Removing layer VI pyramidal neurons that project to the ventral division of the medial geniculate body affects pitch perception that is essential to identify auditory objects by impairing the ability of ferrets to discriminate mistuning tones.

Another descending loop connects the auditory cortex with the inferior colliculus in the midbrain. Silencing optogenetically ArchT-expressing neurons in adult ferrets, we show that within-trial activity in the auditory cortex is required for training-dependent recovery in sound-localization accuracy following monaural deprivation. This learning-induced auditory plasticity requires the functional integrity of the cortico-collicular pathway. The selective elimination of the large coticocollicular pyramidal cells in layer V impairs the ability of animals to adapt to changes in the binaural cue values produced by unilateral ear occlusion.

Beyond their role in unisensory processing, descending cortical loops mediate communication between primary sensory cortical areas. In mice, whiskers stimulation causes suppression of sound-evoked activity in the primary auditory cortex. This suppression is implemented through a descending circuit that links the primary somatosensory cortex, via the auditory midbrain, with thalamic neurons that project to primary auditory cortex.

Those same neural circuits responsible for auditory plasticity in the adult brain are likely to be involved in the generation of tinnitus, a phantom auditory perception. Using optogenetic methods for manipulating brain activity, I am exploring the changes that occur within the auditory cortex when tinnitus is experienced to find out whether those changes can be reversed to alleviate this condition in a clinical context.

Victoria Bajo Lorenzana Biography:

Victoria Bajo Lorenzana was educated at the University of Salamanca in Spain, where she obtained a Bachelor’s degree in Medicine and Surgery and a doctorate (MD PhD) in Neuroscience. She worked as postdoctoral research fellow at the University of Lausanne in Switzerland and back at the University of Salamanca with a Spanish Early Career Award and an EU Human Capital and Mobility Grant. After a brief step in a junior tenured position in Spain, she moved to Oxford with the Millennium when she was awarded a Marie Curie fellowship to work in the Department of Physiology. She works in the Auditory Neuroscience Group mentored by Andy King since 2003. In 2009, the University of Oxford conferred on her the title of University Research Lecturer and in 2014 the title of Associate Professor. She has been approved as Principal Investigator by DPAG Executive Committee in 2015 and she is also Lecturer in Neuroscience at Balliol.

The focus of Victoria’s career from start is auditory plasticity with a robust reputation in the field endorsed by more than 50 papers published and research projects funded, including three times in a row by Deafness Research UK. Her wok has been seminal establishing the role of specific neural circuits, particularly corticofugal connections in sensory perception and learning-induced auditory plasticity. Using a combination of anatomical tracing techniques including gene expression, optogenetics, electrophysiology in vitro and in vivo in awake animal, and operant conditioning behavioural paradigms she has elucidated the essential role of the auditory cortex in perceptual learning. Currently she is investigating the neural circuits responsible for auditory plasticity in the adult brain involved in the generation of tinnitus, a phantom auditory perception. One of her interests is to identify and be able to manipulate neural circuits in the adult brain that contribute to tinnitus and to find out how the condition is affected by sleep.

Dr Richard Tyser: “Form and function in the developing heart”

The heart is the first organ to form and function during development, essential in providing the embryo with oxygen and nutrients. The first morphologically recognisable heart structure in the developing embryo is the cardiac crescent, which forms due to the coordinated addition of cells from multiple different progenitor sources at around embryonic day 8.0 in the mouse. To date, our research has assessed the onset of function and, more recently, focused on mapping the anatomical and transcriptional profile of cardiac progenitors during cardiac crescent formation. This work identified a previously unknown cardiac progenitor population which we termed the Juxta cardiac field (JCF). We found that the JCF could give rise to at least two cardiac-related lineages: cardiomyocytes and the epicardium, providing a paradigm for how the heart forms. We have begun to translate these findings into the human by performing the first transcriptional characterisation of human gastrulation at around 17 days of development, as well as spatially resolving the transcriptional profile of cells in the 3-week-old human heart. Exploring how the heart develops not only addresses questions of fundamental biological significance, but also aids in our understanding of disease; by establishing the underlying causes of disease as well as providing a blueprint for strategies on how best to treat them.

Richard Tyser Biography:

Richard Tyser’s work is focused on understanding how the heart forms and starts to function during embryonic development. To study this he uses a number of different techniques including live time-lapse imaging and single-cell transcriptomics.

He was awarded a BSc degree in Biomedical Science with Industrial Experience from the University of Manchester. During his degree he undertook a placement year at the University of Nevada, Reno (USA) investigating cAMP signalling in cardiomyocytes with Professor Robert Harvey as well as a summer placement studying cardiomyocyte calcium handling with Professor David Eisner.

He then moved to London and completed a British Heart Foundation funded PhD in Cardiovascular Medicine at University College London working with Professor Paul Riley. His PhD studies looked at functional calcium handling during early heart formation and its role in subsequent heart development.

On completion of his PhD, he started postdoctoral studies with Professor Shankar Srinivas at the University of Oxford, working as part of a Wellcome Trust funded consortium to investigate early mammalian lineage decisions. During this time his work focused on using single cell sequencing and imaging to characterise the different cell types that are present in the forming heart.

In 2018, he was awarded a British Heart Foundation Immediate Basic Research Fellowship to study how the first heartbeat is initiated. Overall his hope is that this research will improve our understanding of congenital heart defects and will suggest new strategies to help treat heart disease and arrhythmias.