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Student Neuroscience Seminar with Professor Mu-Ming Poo
April 17 @ 11:00 - 12:30
Student Neuroscience Seminar
Tuesday 17 April @ 11am – 12.30pm (Sherrington Library, Sherrington Building, Department of Physiology, Anatomy and Genetics)
This Tuesday April 17th at 11am, selected DPhil students will present and discuss their current neuroscience research with Gruber Prize in Neuroscience winner Professor Mu-Ming Poo from the Institute of Neuroscience, Shanghai. This will take place at the Sherrington Library, Sherrington Building, Department of Physiology, Anatomy and Genetics. Free lunch and snacks will be provided during/after the event! Please click ‘Read More’ to see the abstracts.
Axonal regulation of striatal dopamine transmission by the GABA transporter
Bradley Roberts – Supervised by Prof Stephanie Cragg,
Dopamine (DA) transmission in the striatum plays an essential role in the physiology of reward seeking, motivation and motor control. In addition to the mechanisms that govern action potential generation in the midbrain, DA release is influenced by a number of presynaptic mechanisms at release sites in the striatum. Membrane GABA transporters (GAT) are expressed on GABAergic neurons in the striatum and function to regulate ambient levels of GABA. Further, GAT is presumably located on DA axons to help sustain GABA co-release, altogether positioning the GAT to locally modulate striatal DA transmission. Here we reveal that GAT inhibition dramatically attenuates nigrostriatal but not mesolimbic DA transmission, which we attribute to differences in GAT expression along the dorsal-ventral axis of the striatum. We find that GAT inhibition increases ambient GABA levels in the striatum, which subsequently acts at GABA receptors on DA axons to decrease probability of release. Furthermore, we confirm GAT immunoreactivity on DA axons and reveal for the first time that ambient GABA clamps DA release in the natural slice. These findings indicate that GAT can powerfully modulate striatal DA release through the regulation of ambient GABA and, as such, has potential implications for psychomotor disorders associated with dysfunction of nigrostriatal DA transmission.
Optogenetic silencing of retrosplenial cortex disrupts sensory associative memory
Ana Bottura de Barros – Supervised by Dr Michael Kohl and Prof David Bannerman
Numerous studies implicate the hippocampus and neocortex in the formation of associative memories. Still, it is unclear how sensory and contextual information is stored in these regions. The retrosplenial cortex (RSC) is known to reciprocally connect to the hippocampal formation and to sensory areas. Although RSC has been previously described as important for processing spatial information, this connectivity suggests that the RSC might be involved in hippocampus-neocortex interplay and more generally required in the formation and storage of sensory associative memory. This notion is supported by RSC-lesion and -inactivation studies that produced impairments in associative memory.
Here, we developed an associative memory task in mice and performed precise optogenetic manipulations of RSC activity to understand its role in facilitating the association of neutral sensory stimuli. We developed an aversive preconditioning paradigm which allows us to test the mechanisms underlying neutral stimuli associations in mice. We used the red-shifted opsin, Jaws, to inactivate the RSC during different phases of the task to investigate the role of this structure in sensory associative learning.
Our results show that control mice successfully learn the preconditioned association in our task. Remarkably, optogenetic silencing of the RSC at the time when the mice form associations between neutral stimuli reduces performance to chance levels.
We are currently characterising synaptic plasticity rules in ex-vivo slices of RSC and optically record changes in RSC activity during exposure to sensory stimuli in vivo.
In summary, we established a new sensory preconditioning task for mice allowing us to probe associative memory of neutral stimuli. Optogenetic silencing of RSC enables us to demonstrate the necessity of the RSC in this type of memory and ongoing work aims at elucidating the underlying synaptic mechanisms.
Dante Wasmuht – Supervised by Prof Kristine Krug
How external stimuli give rise to perceptual decisions has been proposed to depend on the correlated activity of groups of behaviorally relevant neurons. Here, we quantified the shared variability in neuronal firing i.e. spike count correlations (rSC) and perceptual choice signals in visual area V5/MT, while two monkeys (macaca mulata) made perceptual decisions about the direction of rotation of a structure-from-motion cylinder. The average spike count correlation evoked by a perceptually ambiguous cylinder stimulus was high at rSC=0.3 and significantly larger than for a classic zero-coherence motion stimulus, on sites that were recorded under an interleaved design (0.4 vs 0.22). Analysis of the time-scale of correlations revealed that the difference in correlations between the two stimulus paradigms arose at large timescales (hundreds of milliseconds). Interestingly, correlations evoked by non-ambiguous versions of the cylinder were significantly smaller than those for the ambiguous version, approaching the correlation value evoked by random motion stimuli. Focusing on ambiguous cylinder stimuli, we found a positive correlation between the spike count correlations of neurons and their choice-related activity (choice probability; CP). Large choice probabilities were specifically associated with correlations at large time scales (hundreds of milliseconds). Additionally, we found that the time course of choice probabilities was predicted by the time course of correlations on larger timescales but not the instantaneous correlations. Our results suggest that enhanced large timescale correlations and choice probability for the ambiguous cylinder are the neural signature of top-down influences into V5/MT processing, which could convey and stabilize the signals that shape the perceptual appearance of visual stimuli.
Sensory cortex is optimised for prediction of future input
Yosef Singer – Supervised by Prof Andrew King
Neurons in sensory cortex are tuned to diverse features in natural scenes. But what determines which features neurons become selective to? I will explore the idea that neuronal selectivity is optimised to represent features in the recent past of sensory input that best predict immediate future inputs. I tested this hypothesis using simple feedforward neural networks, which were trained to predict the next few video or audio frames in clips of natural scenes. The networks developed receptive fields that closely matched those of real cortical neurons, including the oriented spatial tuning of primary visual cortex, the frequency selectivity of primary auditory cortex and, most notably, in their temporal tuning properties. Furthermore, the better a network predicted future inputs the more closely its receptive fields tended to resemble those in the brain. This suggests that sensory processing is optimised to extract those features with the most capacity to predict future input. These results have been reported in our recent bioRxiv paper: https://www.biorxiv.org/content/early/2017/11/24/224758. I will also present some new results, where I use a hierarchical temporal prediction model to examine neuronal tuning properties at multiple levels of the visual hierarchy.