UH Biocomputation Group - Purkinje cellshttp://biocomputation.herts.ac.uk/2016-02-03T10:56:52+00:00Exploring the cerebellar Purkinje cell2016-02-03T10:56:52+00:002016-02-03T10:56:52+00:00Kirsty Kiddtag:biocomputation.herts.ac.uk,2016-02-03:/2016/02/03/exploring-the-cerebellar-purkinje-cell.html<p class="first last">Kirsty Kidd's journal club session where she summarises her work in investigating changes in the morphology of cerebellar Purkinje cells over different species and the effects of these changes on the cells' ability to process and transfer information.</p>
<p>Purkinje cells are a constant feature of the cerebellar cortex. Though often characterised by their complex dendritic branching, phylogenetically earlier Purkinje cells are much simpler structures. With studies of in vitro electrophysiological behaviour suggesting that firing patterns are very similar across species [1, 2, 3], what has informed such an expensive change in morphology and what effect has this change had on the cells ability to process and transfer information?</p>
<p>This talk will summarise my work in investigating these questions by modelling and analysing Purkinje cells from seven different species.</p>
<p><strong>Date:</strong> 05/02/2016 <br />
<strong>Time:</strong> 16:00 <br />
<strong>Location</strong>: LB252</p>
<p>[1] <a class="reference external" href="http://jn.physiology.org/content/jn/32/6/871.full.pdf">Bloedel J.R. and Llinás R. (1969) Neuronal interactions in frog cerebellum, Journal of neurophysiology, 32(6):871-880</a> <br />
[2] <a class="reference external" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1191918/">Hounsgaard J. and Midtgaard J. (1988) Intrinsic determinants of firing pattern in Purkinje cells of the turtle cerebellum, The Journal of Physiology, 402(1):731-749</a> <br />
[3] <a class="reference external" href="http://science.sciencemag.org/content/160/3832/1132.short">Llinás R., Nicholson C., Freeman A., Hillman D.E. (1968) Dendritic spikes and their inhibition in alligator Purkinje cells, Science, 160(3832):1132-1135</a> <br /></p>
The effect of regularity, synchrony, and STD on deep cerebellar nuclei in physiological conditions and during downbeat nystagmus2015-11-11T16:40:36+00:002015-11-11T16:40:36+00:00Julia Goncharenkotag:biocomputation.herts.ac.uk,2015-11-11:/2015/11/11/the-effect-of-regularity-synchrony-and-std-on-deep-cerebellar-nuclei-in-physiological-conditions-and-during-downbeat-nystagmus.html<p class="first last">Julia Goncharenko's journal club session on the effect of regularity, synchrony, and STD on deep cerebellar nuclei in physiological conditions and during downbeat nystagmus.</p>
<p>It was previously believed, that the reason for downbeat nystagmus (DBN, the symptom of CACNA1a gene mutation) is a lack of inhibition, and that it could be alleviated by an increase of the overall firing rate. It is postulated that 4AP (4-aminopyridine, non-selective voltage-dependent K+ channel blocker) enhances Purkinje cell activity in the flocculus and restores inhibition of anterior canal pathways to a normal level [Glasauer 2005]. But this theory has been disproved by electrophysiological experiments on tg/tg mice cerebellum slices showing that therapeutic concentrations of 4-AP do not increase the inhibitory drive of cerebellar Purkinje cells. Therefore, 4-AP restores the severely diminished precision of pacemaking in Purkinje cells of episodic ataxia type two (EA2, channelopathie, affecting the PQ calcium channel-encoding gene,CACNA1A) mutant mice to normal level by prolonging and increasing the action potential after hyperpolarization [Alvin˜a and Khodakhah, 2010]. In other word, the main consequence of tg/tg chanelopathy is an increase of spike irregularity.</p>
<p>The recent electrophysiological findings encouraged German scientists to reconsider their previous findings by investigating the potential
effect of changing the cerebellar output of Purkinje cells (PC, class of GABAergic neurons located in the cerebellum which plays a fundamental role in controlling motor movement) regularity in the vestibular nuclei in a modelling study [Glasauer 2011]. Their first result was that only regularity together with synchrony would have a significant effect on the postsynaptic target neuron. But these results are incompatible with their system-level model, as well as with the current view on the nature of DBN.</p>
<p>Neither the population level model [Glasauer et al, 2008] nor the conductance-based model of a single neuron [Glasauer et al, 2011] appeared able to explain the electrophysiological findings.</p>
<p>The main assumption is that their model didn't give the correct results due to not taking into an account the effect of short-term depression (STD). In my findings, there is no significant difference in data with the presence or absence of STD. But difference in firing rate with the presence and absence of STD becomes significant for higher noise levels. I assume, that such a small difference in noise levels between wild-type and tg/tg could be explained taking into account the way, how known CV values for wild-type and tg/tg mice were converted to noise. Noise levels were obtained after building a dependency graph of CV form
noise.</p>
<p><strong>Date:</strong> 13/11/2015 <br />
<strong>Time:</strong> 16:00 <br />
<strong>Location</strong>: LB252</p>