UH Biocomputation Group - Humanshttp://biocomputation.herts.ac.uk/2023-07-04T22:47:17+01:00Predicting saccades given the behavior of Purkinje cells2023-07-04T22:47:17+01:002023-07-04T22:47:17+01:00Eleonora Bernasconitag:biocomputation.herts.ac.uk,2023-07-04:/2023/07/04/predicting-saccades-given-the-behavior-of-purkinje-cells.html<p class="first last">Eleonora Bernasconi's Journal Club session where she will talk about her work in the talk entitled "Predicting saccades given the behavior of Purkinje cells".</p>
<p>On this week's Journal Club session, Eleonora Bernasconi will talk about her work in the talk entitled "Predicting saccades given the behavior of Purkinje cells".
Please see below for the abstract of a supporting paper.</p>
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<p>A better understanding of the neural and functional mechanisms underlying drug-induced
changes in pathological nystagmus is likely to improve medical treatment. A treatment
option for downbeat nystagmus (DBN), a common form of acquired fixation nystagmus that
often occurs with cerebellar degeneration, is low doses of the potassium channel blocker
4-aminopyridine (4-AP). The upward ocular drift in DBN has a spontaneous and a vertical
gaze-evoked component. Detailed analysis of the effect of 4-AP in patients showed that the
drug consistently improved the gaze-evoked component, but had less effect in reducing the
spontaneous drift. We show by a combination of computational modelling at the systems
level and at the neuronal level how this differential effect can be investigated. We have
previously postulated that DBN is caused by damage to the floccular lobe (FL). 4-AP, which
has been shown to increase the excitability of Purkinje cells (PCs) in slice experiments,
may thus suppress DBN by partly restoring floccular function. We simulated the effect of
low concentrations of 4-AP on the cellular level using a multicompartment model of a PC,
in which we changed ion channel properties to simulate damage. The transition from the
cellular level to the systems level was achieved by constructing a population response.
Systems level modelling predicted that the effect of 4-AP on the PCs should reduce DBN,
but the predicted effect on the gaze-dependent component was less than is observed in
patients. Our results suggest that the beneficial effect of 4-AP on DBN cannot be solely
explained by its effect at the neuronal level of PCs, and suggests added effects at the
level of the population of neurons.</p>
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<p>Papers:</p>
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<li>S. Glasauer, C. Rössert, <a class="reference external" href="https://doi.org/10.1016/S0079-6123(08)00675-4">"Modelling drug modulation of nystagmus"</a>, 2008, Progress in Brain Research, 171, 527--534</li>
<li>S. Glasauer, <a class="reference external" href="https://doi.org/10.1196/annals.1303.018">"Cerebellar contribution to saccades and gaze holding: a modeling approach"</a>, 2003, Annals of the New York Academy of Sciences, 1004, 206--219</li>
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<p><strong>Date:</strong> 2023/07/07 <br />
<strong>Time:</strong> 14:00 <br />
<strong>Location</strong>: online</p>
Computational model of the cerebellar cortex2023-05-17T17:18:16+01:002023-05-17T17:18:16+01:00Eleonora Bernasconitag:biocomputation.herts.ac.uk,2023-05-17:/2023/05/17/computational-model-of-the-cerebellar-cortex.html<p class="first last">Eleonora Bernasconi's Journal Club session where she will talk about a her work "Computational model of the cerebellar cortex".</p>
<p>This week on Journal Club session Eleonora Bernasconi will present her work about "Computational model of the cerebellar cortex". Please find below to see the abstract of one of the related papers.</p>
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<p>Climbing fibers (CFs) provide instructive signals driving cerebellar learning, but
mechanisms causing the variable CF responses in Purkinje cells (PCs) are not fully
understood. Using a new experimentally validated PC model, we unveil the ionic mechanisms
underlying CF-evoked distinct spike waveforms on different parts of the PC. We demonstrate
that voltage can gate both the amplitude and the spatial range of CF-evoked Ca2+ influx by
the availability of K+ currents. This makes the energy consumed during a complex spike
(CS) also voltage dependent. PC dendrites exhibit inhomogeneous excitability with
individual branches as computational units for CF input. The variability of somatic CSs
can be explained by voltage state, CF activation phase, and instantaneous CF firing rate.
Concurrent clustered synaptic inputs affect CSs by modulating dendritic responses in a
spatially precise way. The voltage- and branch-specific CF responses can increase
dendritic computational capacity and enable PCs to actively integrate CF signals.</p>
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<p>Papers:</p>
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<li>Y. Zang, S. Dieudonn'e, E. De, Schutter, <a class="reference external" href="https://doi.org/10.1016/j.celrep.2018.07.011">"Voltage- and Branch-Specific Climbing Fiber Responses in Purkinje Cells"</a>, 2018, Cell Reports, 24, 1536--1549</li>
<li>S. Sudhakar, S. Hong, I. Raikov, R. Publio, C. Lang, T. Close, D. Guo, M.
Negrello, E. De, Schutter, <a class="reference external" href="https://doi.org/10.1371/journal.pcbi.1005754">"Spatiotemporal Network Coding of Physiological
Mossy Fiber Inputs by the Cerebellar Granular Layer"</a>, 2017, PLoS computational
biology, 13, e1005754</li>
</ul>
<p><strong>Date:</strong> 2023/05/19 <br />
<strong>Time:</strong> 14:00 <br />
<strong>Location</strong>: online</p>