Cerebellum-dependent learning:an examination of memory consolidation processes and roles for the monoamine systems
Christopher Yeo (University College London, UK)
Simple forms of cerebellum-dependent motor learning, such as eyeblink conditioning (EBC), are good models to investigate how intelligent behaviour emerges from an identified neural network.Studies have shown that normal function within both cerebellar cortex and cerebellar nuclei is essential for the acquisition and expression of EBC learning but reversible inactivations of the cortical and nuclear control regions have revealed that consolidation and storage of this motor memory is essentially cortical.The findings are consistent with a recent model suggesting that the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent.There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in EBC, remains mainly dependent upon cortical memory storage. Electrophysiological studies have suggested a variety of candidate cerebellar neural plasticities that might underlie behavioural learning. Few, however, have analyzed the consolidation phase when the memories would normally be stabilized. New evidence now reveals that EBC consolidation can be disturbed profoundly by application of atenolol, a β1-adrenoceptor antagonist, to the cerebellar cortex, consistent with an early theory (Gilbert 1975) that cerebellar learning requires a noradrenaline signal for consolidation.Learning was significantly impaired in subjects that received infusions of the selective β1antagonist atenolol immediately after each of two training sessions but it was unimpaired in those that received atenolol infusions two hours post-training. Immunohistochemistry was used to map the distribution of β1 and β2-adrenoceptors and of noradrenergic afferents in the cerebellar cortex. A sharp dissociation of β1- and β2-adrenoceptors in the cerebellar cortex was seen. β1-adrenoceptor protein is entirely restricted to Purkinje cells whereas β2-adrenoceptor protein was almost completely restricted to Bergmann glia soma and processes, with very low levels in some Purkinje cells.In the cortical vermis, individual noradrenergic beaded afferents were seen to travel with limited medial-lateral extents (less than 250 microns) but with much longer rostro-caudal extents (up to 1mm and potentially longer), approximately consistent with the dimensions of individual cortical microzones. We conclude that noradrenaline provides an important consolidation signal for cerebellum-dependent learning in the two hours following training, that the noradrenergic afferents may target limited cortical territories and that the essential mechanism involves β1-adrenoceptors on Purkinje cells. That consolidation of amygdala-dependent fear memories and of hippocampus-dependent spatial memories are similarly sensitive to noradrenergic modulation strongly supports the suggestion that there is significant conservation of memory consolidation mechanisms across multiple brain regions.
Vendredi 3 mars 2017 à 11h30, Salle de conférence.
Seeing Colours, Feeling the Light: Probing the Visual and Non-visual Systems with Spectrally Tuneable Light
Anya Hurlbert (Newcastle University, UK)
Light shapes human behaviour, through both conscious perception and unconscious sensing of the environment. Variations in illumination spectra – the colour of light – are abundant in the natural and man-made worlds, and are important signals for both the visual and non-visual systems. The perceptual phenomenon of colour constancy – fundamental to colour perception and its role in object recognition - depends on the human visual system “discounting” spectral variations in illumination, so that we may recognise bananas as ripe yellow in twilight or bright sunshine, for example. The non-visual system monitors changes in light spectra to set biological rhythms and moods. Both systems originate in retinal light sensors – cones, rods, and intrinsically photosensitive retinal ganglion cells – whose spectral sensitivities and projection pathways partially overlap. Thus, the effects of spectral variations in light on the two systems interact. In this talk, I will describe a series of experiments which investigate these effects in humans, using spectrally tuneable light sources. We find, for example, that making lights “bluer”, for example, improves colour constancy, but leads to poorer performance on visual attention tasks and worse mood in the evening, despite increasing alertness.
Vendredi 10 mars 2017 à 11h30, Salle de conférence.
Brain energy metabolism assessed by genetically encoded sensors for metabolites
Johannes Hirrlinger, Carl-Ludwig-Institute for Physiology, Leipzig, Germany
To provide proper maintenance of brain function appropriate supply of energy is essential. Deficiency of energy delivery as e.g. during stroke or other injuries in the central nervous system will very quickly severely impair brain activity. Also during normal brain function, brain energy metabolism involves complex interactions of different types of brain cells. This metabolic cooperation between different types of brain cells has been a major topic of research in brain energy metabolism for many years focussing mainly on astrocytes and neurons for a long time and only recently also oligodendrocytes have entered the stage. To address the dynamics of metabolites within cells at an appropriate high spatial and temporal resolution we employed genetically encoded fluorescent sensors for metabolites like ATP, glucose, lactate as well as the NAD^+ /NADH-redox stateto follow the concentration of these metabolic parameters in real time in specific cell types both in vitro as well in tissue preparations. For example,using a novel transgenic mouse line expressing a sensor for ATP in neurons and an experimental setup allowing electrophysiology and confocal imaging of excised optic nerves simultaneously, we obtained novel insight into physiological but also pathophysiological axon-glia interactions in this well myelinated fiber tract. Furthermore, we now investigate the dynamics of several parameters of astrocyte metabolism. In summary, genetically encoded sensors for metabolites are powerful tools for an in depth analysis of metabolism and its regulation
Vendredi 31 mars 2017 à 11h30, Salle de conférence.
Rescuing deficits in neuronal plasticity after mild TBI
Barclay Morrison III, Columbia University, USA
Traumatic brain injury (TBI) continues to be a major socio-economic problem with about 2 million head injuries in the US annually, the majority being mild in severity.To understand better the mechanisms of TBI, we have developed in vitro models using organotypic brain slice cultures that afford precise control over injury biomechanics.With these models, we have previously developed tolerance criteria to determine safe levels of exposure that could be used to engineer better safety systems to prevent TBI.More recently, we have focused on how different mechanical stimuli (injury) may alter neuronal activity and electrophysiological function within hippocampal neuronal networks and explored therapeutic strategies to reverse pathological changes.Our recent findings suggest that after mild TBI, a disruption of dendritic organization may underlie deficits in long-term potentiation, i.e. the cellular correlates of learning and memory.We have identified therapeutic interventions that rescue LTP with therapeutic windows as long as 6 hours after injury.The long-term goal of our research is to reduce the socio-economic costs of TBI by developing novel treatments and by helping others engineer better protection systems.
Vendredi 28 avril 2017 à 11h30, Salle de conférence.
Probing neural circuits with shaped light
Na Ji (Janelia Research Campus, USA)
To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional relationships between individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter dimensions with sub-micron spatial resolution. I will describe how we use concepts in astronomy and optics to develop next-generation microscopy methods for imaging neural circuits at higher resolution, greater depth, and faster speed. By shaping the wavefront of the light, we have achieved synapse-level spatial resolution through the entire depth of primary visual cortex, optimized microendoscopes for imaging deeply buried nuclei, and developed a video-rate (30 Hz) volumetric imaging method. We apply these methods to understanding neural circuits, using the mouse primary visual cortex as our model system.
Vendredi 19 mai 2017 à 11h30, Salle de conférence.