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Multiplication by NMDA receptors in Direction Selective Ganglion cells (Poleg-Polsky & Diamond 2016)

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<div class=WordSection1>

<p class=MsoNormal><b style='mso-bidi-font-weight:normal'>Model of
multiplication in direction selective ganglion cells<o:p></o:p></b></p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal><a href="http://www.ncbi.nlm.nih.gov/pubmed/26948896"><span
style='color:windowtext;text-decoration:none;text-underline:none'>NMDA
Receptors Multiplicatively Scale Visual Signals and Enhance Directional Motion
Discrimination in Retinal Ganglion Cells.</span></a> Poleg-Polsky&nbsp;A,
Diamond JS. Neuron. 2016 Mar 16;89(6):1277-90. <span class=SpellE>doi</span>:
10.1016/j.neuron.2016.02.013. <span class=SpellE>Epub</span> 2016 Mar 3. PMID:26948896</p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal>The simulation models synaptic integration in a
multi-compartmental direction selective ganglion cell (DSGC).</p>

<p class=MsoNormal>The simulated DSGC receives 3 types of <span class=GramE>synaptic<span
style='mso-spacerun:yes'>&nbsp; </span>inputs</span>: </p>

<p class=MsoListParagraphCxSpFirst style='text-indent:-.25in;mso-list:l0 level1 lfo1'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>(1)<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;
</span></span></span><![endif]>Glutamatergic drive, mediated by AMPA and NMDA
receptors</p>

<p class=MsoListParagraphCxSpMiddle style='text-indent:-.25in;mso-list:l0 level1 lfo1'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>(2)<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;
</span></span></span><![endif]>Cholinergic drive, mediated by nicotinic
receptors</p>

<p class=MsoListParagraphCxSpLast style='text-indent:-.25in;mso-list:l0 level1 lfo1'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>(3)<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;
</span></span></span><![endif]>GABAergic drive, mediated by GABAA receptors</p>

<p class=MsoNormal>The drives are activated in a spatial sequence, to imitate a
moving stimulus. Preferred direction (PD) and null direction (ND) are different
in the intensity of the synaptic drives. For tuned inhibition, the inhibitory
drive is 300% larger in the ND. For tuned excitation, the cholinergic drive is
larger by 300% in the PD. In all simulations the number of active glutamatergic
synapses is similar between directions.</p>

<p class=MsoNormal>Three conditions are explored:</p>

<p class=MsoListParagraphCxSpFirst style='text-indent:-.25in;mso-list:l1 level1 lfo2'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>1.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;
</span></span></span><![endif]>Control simulation, with tuned inhibition and
voltage dependent NMDAR behavior</p>

<p class=MsoListParagraphCxSpMiddle style='text-indent:-.25in;mso-list:l1 level1 lfo2'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>2.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;
</span></span></span><![endif]>Zero Mg++ simulation, with tuned inhibition and
voltage insensitive NDMARs</p>

<p class=MsoListParagraphCxSpLast style='text-indent:-.25in;mso-list:l1 level1 lfo2'><![if !supportLists]><span
style='mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin'><span
style='mso-list:Ignore'>3.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;
</span></span></span><![endif]>Tuned excitation simulation, with voltage
dependent NMDAR behavior</p>

<p class=MsoNormal>In each condition clicking on the corresponding button with
run either the PD or ND simulations.</p>

<p class=MsoNormal>NMDARs and voltage gated channels can be 'blocked' by
unchecking the corresponding check boxes.</p>

<p class=MsoNormal>Figure 1: Control condition, PD activation w/ (black) an w/<span
class=GramE>o<span style='mso-spacerun:yes'>&nbsp; </span>(</span>gray) NMDARs
(spikes blocked)</p>

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<p class=MsoNormal>Figure 2: Control condition, ND activation w/ (black) an w/<span
class=GramE>o<span style='mso-spacerun:yes'>&nbsp; </span>(</span>gray) NMDARs
(spikes blocked)</p>

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<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal>In the control case NMDARs amplify the response by about
100%, indicative of multiplication.</p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal>Voltage independent NMDARs amplify both PD (Figure 3) and ND
(Figure 4) responses. The contribution of NMDARs becomes similar between PD and
ND, indicative of additive scaling.</p>

<p class=MsoNormal>Figure 3: Voltage independent NMDARs, PD activation w/
(black) an w/o (gray) NMDARs (spikes blocked)</p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal><span style='mso-no-proof:yes'><!--[if gte vml 1]><v:shape
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</v:shape><![endif]--><![if !vml]><img border=0 width=312 height=260
src="readme.fld/image006.png" v:shapes="Picture_x0020_4"><![endif]></span></p>

<p class=MsoNormal>Figure 4: Voltage independent NMDARs, ND activation w/
(black) an w/o (gray) NMDARs (spikes blocked)</p>

<p class=MsoNormal><span style='mso-no-proof:yes'><!--[if gte vml 1]><v:shape
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 <v:imagedata src="readme.fld/image007.png" o:title=""/>
</v:shape><![endif]--><![if !vml]><img border=0 width=312 height=260
src="readme.fld/image008.png" v:shapes="Picture_x0020_5"><![endif]></span></p>

<p class=MsoNormal><o:p>&nbsp;</o:p></p>

<p class=MsoNormal>Similar additive scaling is observed with tuned excitation:</p>

<p class=MsoNormal>Figure 5: Tuned excitation, PD activation w/ (black) an w/o
(gray) native NMDARs (spikes blocked)</p>

<p class=MsoNormal><span style='mso-no-proof:yes'><!--[if gte vml 1]><v:shape
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src="readme.fld/image010.png" v:shapes="Picture_x0020_6"><![endif]></span><span
style='mso-spacerun:yes'>&nbsp;</span></p>

<p class=MsoNormal>Figure 6: Tuned excitation, ND activation w/ (black) an w/o
(gray) native NMDARs (spikes blocked)</p>

<p class=MsoNormal><span style='mso-no-proof:yes'><!--[if gte vml 1]><v:shape
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<p class=MsoNormal><o:p>&nbsp;</o:p></p>

</div>

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Multiplication by NMDA receptors in Direction Selective Ganglion cells (Poleg-Polsky & Diamond 2016)

modeldb.science/189347

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neuron-simulator retina-ganglion-glu-cell direction-selectivity-synaptic-integration-vision

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