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

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Accession:244262
"... 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."
Reference:
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]
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;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Deep brain stimulation; Evoked LFP;
Implementer(s): Kumaravelu, Karthik [kk192 at duke.edu];
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;
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cEP_stndbs_4.5hz
hoc
balcomp.hoc *
defvar.hoc *
lbcreate.hoc *
mscreate.hoc *
parlib.hoc
parlib2.hoc *
traubcon.hoc *
traubcon_net.hoc *
                            
objref netstims, netstim_netcons, netstim_randoms, netstim_syns
netstims = new List()
netstim_syns = new List()
netstim_netcons = new List()
netstim_randoms = new List()
netstim_random_seedoffset = ranseedbase + pnm.ncell // increment by number of Cells
splitbit = 2^28

func targetcomp_exists() {local spgid
	if (load_balance_phase == 3 || load_balance_phase == 7) {
		spgid = thishost_gid($1)
		if (spgid < 0) { return -1 }
		if (pc.gid_exists(spgid)) {
			if (section_exists("comp", $2, pc.gid2obj(spgid))) {
				return spgid
			}
		}
	}else{
		if (pc.gid_exists($1)) {
			return $1
		}
	}
	return -1
}

func target_exists() {local spgid
	if (load_balance_phase == 3 || load_balance_phase == 7) {
		spgid = thishost_gid($1)
		if (spgid < 0) { return -1 }
		if (pc.gid_exists(spgid)) {
			return spgid
		}
	}else{
		if (pc.gid_exists($1)) {
			return $1
		}
	}
	return -1
}

proc par_netstim_create() {local gid  localobj cell, syn, nc, ns, r
	if (!use_ectopic) { return }
	if ((gid = targetcomp_exists($1, $2)) >= 0) {
		cell = pc.gid2obj(gid)
		cell.comp[$2] {syn = new PulseSyn(.5)}
		netstim_syns.append(syn)
		syn.amp = $3
		ns = new S_NetStim()
		ns.pp.interval = $4
		netstims.append(ns)
		nc = new NetCon(ns.pp, syn)
		netstim_netcons.append(nc)
		nc.delay = 0
		r = new Random()
		r.negexp(1)
//		r.Isaac64(netstim_random_seedoffset + netstim_base_)
		r.MCellRan4(netstim_random_seedoffset + 1000*netstim_base_)
		ns.pp.noiseFromRandom(r)
		netstim_randoms.append(r)
	}
	netstim_base_ += 1
}

begintemplate gGap
proc init() {
	execerror("gGap not available. use gGapPar instead.", "")
}
endtemplate gGap

objref par_gaps
par_gaps = new List()
gap_src_gid = 2

objref rangap
if (one_tenth_ncell) {
	rangap = new Random()
	rangap.MCellRan4(1)
	rangap.uniform(0,1)
	ranfrac=.1
}

proc par_gap_create() { local gid
	if (!use_gap) { return }
	if (object_id(rangap)) {
		if (rangap.repick() > ranfrac) { return }
	}
	gap_src_gid += 2
	if ((gid = targetcomp_exists($1, $2)) >= 0) {
		par_gap_create1(gid, $2, gap_src_gid + 1, gap_src_gid, $5)
	}
	if ((gid = targetcomp_exists($3, $4)) >= 0) {
		par_gap_create1(gid, $4, gap_src_gid, gap_src_gid + 1, $5)
	}
}
proc par_gap_create1() {localobj c, g
	c = pc.gid2obj($1)
	c.comp[$2] {
		g = new gGapPar(.5)
		par_gaps.append(g)
		pc.target_var(g, &g.vgap, $3)
		pc.source_var(&v(.5), $4)
		g.g = $5
	}
}

icdel0_ = 0
cdel0_ = 0

func nc_append() {local targid, comp  localobj cell, syn, s
	targid = target_exists($2)
	if ($5 <= 0) {
//		if (targid >= 0) {
//			print pc.id, $1, $2, targid, $3, $4, $5, " ", pc.gid2obj(targid)
//		}
		if (icdel0_ == 0) if ((pc.gid_exists($1)!=0) != (targid != 0)) {
if (pmesg) print "Notice: Requesting an interprocessor connection delay of 0"
			icdel0_ = 1
		}
		if (cdel0_ == 0) {
if (pmesg) print "Notice: Requesting a connection delay of 0. Setting those to 1ms."
			cdel0_ = 1
		}
		$5 = 1
	}
	if ($5 < mindelay_) if (pc.gid_exists($1) == 0) if (targid >= 0) {
		mindelay_ = $5
	}

	if (targid >= 0) {
		cell = pc.gid2cell(targid)
		syn = cell.synlist.object($3)
		s = new String()
		classname(syn, s.s)
		if (strcmp(s.s, "GABAA") == 0) {
			syn.e = vgaba.x[cell.type]
		}
		// for debugging :need to switch the debug lines in
		// ampa.mod, traub_nmda.mod, and gabaa.mod
	    if (0) {
		syn.get_loc
		comp = -1
		sscanf(secname(), "%*[^0-9]%*d%*[^0-9]%d",&comp)
		pop_section()
		syn.srcgid = $1
		syn.targid = $2
		syn.synid = $3
		syn.comp = comp
	    }
	}
	if (targid >= 0) {
		return pnm.nc_append($1, targid, $3, $4, $5)
	}else{
		return -1
	}
}

proc set_const_curr_inj() {local i, gid  localobj c, clmp
	if (!use_inject) { return }
	for i = 1, $2 if ((gid = targetcomp_exists($1+i, 1)) >= 0) {
		c = pc.gid2obj(gid)
		c.comp[1] clmp = new IClamp_const(0.5)
		clmp.amp = $o3.x[i]
		iclamp_const_list.append(clmp)
	}
}

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