Deconstruction of cortical evoked potentials generated by subthalamic DBS (Kumaravelu et al 2018)

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"... High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) suppresses parkinsonian motor symptoms and modulates cortical activity. ... Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal was to determine the neural origin of cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA lesioned parkinsonian rats. Second, we used a biophysically-based model of the thalamocortical network to deconstruct the neural origin of the cEP. The in vivo cEP included short (R1), intermediate (R2) and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. R1 was generated by antidromic activation of layer 5 pyramidal neurons, while recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced R2. R3 was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cEP by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms."
1 . Kumaravelu K, Oza CS, Behrend CE, Grill WM (2018) Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation. J Neurophysiol 120:662-680 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex; Thalamus;
Cell Type(s): Neocortex M1 L6 pyramidal corticothalamic GLU cell; Neocortex M1 L5B pyramidal pyramidal tract GLU cell; Neocortex M1 L4 stellate GLU cell; Hodgkin-Huxley neuron; Neocortex layer 4 neuron; Neocortex fast spiking (FS) interneuron; Neocortex primary motor area pyramidal layer 5 corticospinal cell;
Channel(s): I Na,p; I K; I Sodium; I_KD; I Calcium; I T low threshold; I L high threshold; I_AHP;
Gap Junctions: Gap junctions;
Receptor(s): AMPA; Gaba; NMDA;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Deep brain stimulation; Evoked LFP;
Implementer(s): Kumaravelu, Karthik [kk192 at];
Search NeuronDB for information about:  Neocortex M1 L6 pyramidal corticothalamic GLU cell; Neocortex M1 L5B pyramidal pyramidal tract GLU cell; Neocortex M1 L4 stellate GLU cell; AMPA; NMDA; Gaba; I Na,p; I L high threshold; I T low threshold; I K; I Sodium; I Calcium; I_AHP; I_KD; Gaba; Glutamate;
alphasyndiffeq.mod *
alphasynkin.mod *
alphasynkint.mod *
ampa.mod *
ar.mod *
cad.mod *
cal.mod *
cat.mod *
cat_a.mod *
gabaa.mod *
iclamp_const.mod *
k2.mod *
ka.mod *
ka_ib.mod *
kahp.mod *
kahp_deeppyr.mod *
kahp_slower.mod *
kc.mod *
kc_fast.mod *
kdr.mod *
kdr_fs.mod *
km.mod *
naf.mod *
naf_tcr.mod *
naf2.mod *
nap.mod *
napf.mod *
napf_spinstell.mod *
napf_tcr.mod *
pulsesyn.mod *
rampsyn.mod *
rand.mod *
ri.mod *
traub_nmda.mod *
balanal.hoc *
balcomp.hoc *
cell_templates.hoc *
clear.hoc *
finit.hoc *
fortmap.hoc *
gidcell.hoc * *
onecell.hoc * *
prcellstate.hoc *
printcon.hoc *
spkplt.hoc *
vclampg.hoc *
vcompclamp.hoc *
vcompsim.hoc *
Traub-like NMDA synaptic current
This file is a merge of rampsyn.mod and expsyn.mod
The Traub et al 2005 paper contains a nmda synaptic current which
when activated has a linear ramp (in conductance) up to the conductance scale
over 5ms, then there is an exponential decay (in conductance).
Tom Morse, Michael Hines
	RANGE tau, time_interval, e, i,weight, NMDA_saturation_fact, flag, g
	GLOBAL gfac
: for network debugging
:	USEION nmda1 WRITE inmda1 VALENCE 0
:	USEION nmda2 WRITE inmda2 VALENCE 0
:	RANGE srcgid, targid, comp, synid

	(nA) = (nanoamp)
	(mV) = (millivolt)
	(uS) = (microsiemens)
	(mM) = (milli/liter)

	tau = 130.5 (ms)  <1e-9,1e9>	: NMDA conductance decay time constant
: default choice is tauNMDA_suppyrRS_to_suppyrRS=130.5e0, a sample tau from groucho.f
	time_interval = 5 (ms) <1e-9,1e9>
	e = 0	(mV)
	weight = 2.5e-8 (uS)	: example conductance scale from Traub 2005 et al
			 	: gNMDA_suppyrRS_to_suppyrRS (double check units)
	NMDA_saturation_fact= 80e0 (1) : this saturation factor is multiplied into
		: the conductance scale, weight, for testing against the
		: instantaneous conductance, to see if it should be limited.
: FORTRAN nmda subroutine constants and variables here end with underbar 
	A_ = 0 (1) : initialized with below in INITIAL, assigned in each integrate_celltype.f
	BB1_ = 0 (1) : assigned in each integrate_celltype.f
	BB2_ = 0 (1) : assigned in each integrate_celltype.f
	Mg = 1.5 (mM) : a FORTRAN variable set in groucho.f
	gfac = 1

	v (mV)
	i (nA)
	event_count (1)	: counts number of syn events being processed
	k (uS/ms) : slope of ramp or 0
	g (uS)
	A1_ (1)
	A2_ (1)
	B1_ (1)
	B2_ (1)
	Mg_unblocked (1)
:	inmda1 (nA)
:	inmda2 (nA)
:	srcgid
:	targid
:	comp
:	synid

	A (uS)
	B (uS)

	A_ =  exp(-2.847)  : assigned in each integrate_celltype.f
	BB1_ = exp(-.693)  : assigned in each integrate_celltype.f
	BB2_ = exp(-3.101) : assigned in each integrate_celltype.f
	g = 0
	A = 0
	B = 0
	k = 0

	SOLVE state METHOD cnexp
	g = A + B
	if (g > NMDA_saturation_fact * weight) { g = NMDA_saturation_fact * weight }
	g = g*gfac
	i = g*Mg_unblocked*(v - e)
:	inmda1 = g
:	inmda2 = -g

	B' = -B/tau
	A' = k

NET_RECEIVE(weight (uS)) {
	if (flag>=1) {
		: self event arrived, terminate ramp up
	: remove one event's contribution to the slope, k
		k = k - weight/time_interval
	: Transfer the conductance over from A to B
		B = B + weight
		A = A - weight
	} else {
		: stimulus arrived, make or continue ramp
		net_send(time_interval, 1) : self event to terminate ramp
	: add one event ramp to slope k:
		k = k + weight/time_interval
:	note there are no state discontinuities at event start since the begining of a ramp
:	only has a discontinuous change in derivative

: an NMDA subroutine converted from FORTRAN whose sole purpose was to compute the number
: of open nmda recpt channels due to relief from Mg block

PROCEDURE Mg_factor() {
           A1_ = exp(-.016*v - 2.91)
           A2_ = 1000.0 * Mg * exp (-.045 * v - 6.97)
           B1_ = exp(.009*v + 1.22)
           B2_ = exp(.017*v + 0.96)
           Mg_unblocked  = 1.0/(1.0 + (A1_+A2_)*(A1_*BB1_ + A2_*BB2_) /
                 (A_*A1_*(B1_+BB1_) + A_*A2_*(B2_+BB2_))  )