Rhesus Monkey Layer 3 Pyramidal Neurons: Young vs aged PFC (Coskren et al. 2015)

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Accession:168858
Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. Tuning passive parameters for each model predicted significantly higher membrane resistance (Rm) in aged versus young neurons. This Rm increase alone did not account for the empirically observed fI-curves, but coupling these Rm values with subtle differences in morphology and membrane capacitance Cm did. The predicted differences in passive parameters (or other parameters with similar effects) are mathematically plausible, but must be tested empirically.
Reference:
1 . Coskren PJ, Luebke JI, Kabaso D, Wearne SL, Yadav A, Rumbell T, Hof PR, Weaver CM (2015) Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. J Comput Neurosci 38:263-83 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Influence of Dendritic Geometry; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s;
Implementer(s): Weaver, Christina [christina.weaver at fandm.edu];
Search NeuronDB for information about:  Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell; I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
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CoskrenEtAl2015
HHmodel
Scripts
hoc
x86_64
.libs
kvz_nature.mod *
max.mod *
naz_nature.mod *
origlen.mod *
peak.mod *
vsource.mod *
kvz_nature.c *
kvz_nature.lo *
libnrnmech.la *
max.c *
max.lo *
mod_func.c *
mod_func.lo *
naz_nature.c *
naz_nature.lo *
origlen.c *
origlen.lo *
peak.c *
peak.lo *
special *
vsource.c *
vsource.lo *
                            
TITLE peak.mod

COMMENT 
pk: record peak time and peak value of membrane potential
Michael Hausser & Arnd Roth                     25.9.1997
Philipp Vetter	modified last			30.12.1998

vpeak/tpeak are locked to first peak
dvdt2 is for time t - 2*dt
AP measurements		dvdtmax, dvdtmaxII, onset, vonset, halfwidth, vhalf, vrest, dVdr
electrotonic lengths	X, Xsec
impedance mismatch	Zmismatch, Rmismatch, aZmismatch, aRmismatch, f

Copyright (C) 2001  Philipp Vetter, Arnd Roth and Michael Hausser

This program is free software; you can redistribute it and/or
modify it under the terms of the GNU General Public License
as published by the Free Software Foundation; either version 2
of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful,
but WITHOUT ANY WARRANTY; without even the implied warranty of
MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
GNU General Public License for more details.

You should have received a copy of the GNU General Public License
along with this program; if not, write to the Free Software
Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA  02111-1307, USA.
ENDCOMMENT

UNITS {
	(mV) = (millivolt)
	(Mohms) = (megohms)
}

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX pk
	RANGE tpeak, vpeak, vpeakm
	RANGE dvdtpeak, dvdt2peak, onset_ref, onset, vonset, halfwidth, vhalf, vrest, dvdr
	RANGE Zmismatch, Rmismatch, aZmismatch, aRmismatch, f
	RANGE Zback, Rback, aZback, aRback
	RANGE Zfwd, Rfwd, aZfwd, aRfwd
	RANGE Z, R, aZ, aR
	RANGE Xsec, Xfrc, Xlen, Xo, sign
	RANGE dvdt2
}

PARAMETER {
	vhalf (mV)
	v (mV)
	dt (ms)
}

ASSIGNED {
	tpeak (ms)
	vpeak (mV)
	vpeakm (mV)
	dvdt (ms)
	dvdt2 (mV/ms*ms)
	dvdt2peak (mV/ms*ms)
	dvdtpeak (mV/ms)
	onset_ref (mV/ms)
	onset (ms)
	v1 (mV)
	v2 (mV)
	v3 (mV)
	vonset (mV)
	halfwidth (ms)
	below
	below_old
	upstroke (ms)
	downstroke (ms)
	dvdr     (mv/micron)
	vrest (mV)
	Rmismatch     (1)
	Zmismatch     (1)
	Rback   (Mohm)
	Zback   (Mohm)
	Rfwd    (Mohm)
	Zfwd    (Mohm)
	R     	(Mohm)
	Z     	(Mohm)


	aRmismatch  (1)
	aZmismatch  (1)
	aRback  (Mohm)
	aZback  (Mohm)
	aRfwd   (Mohm)
	aZfwd   (Mohm)
	aR     	(Mohm)
	aZ     	(Mohm)




	f     (0.001/ms)
	Xo 	(1)
	Xlen    (1)
	Xsec	(1)
	Xfrc	(1)
	sign	(1)
}

INITIAL {
	tpeak = 0 (ms)
	vpeak = -100 (mV)
	vpeakm = -100 (mV)
	onset = 0    (ms)
	dvdtpeak  = 0 (mV/ms)
	dvdt2peak  = 0 (mV/ms)
	downstroke = 0 (ms)
	upstroke   = 0 (ms)
	vrest = v
	check()
}

BREAKPOINT {	SOLVE check  }


PROCEDURE check() {
			if (v > vpeak && vpeakm==-100) { tpeak = t
					 		 vpeak = v }

			if (v+4 < vpeak) { vpeakm = 1 }

			v1        = v2
			v2        = v3
			v3        = v
		        dvdt	  = (v3 - v2)/(dt)
			dvdt2	  = (v3 - 2*v2 +v1)/(dt*dt)

			if (dvdt > dvdtpeak) 			      	{ dvdtpeak = dvdt }
			if (dvdt2 > dvdt2peak) 			      	{ dvdt2peak = dvdt2 }

			if (dvdt > onset_ref && onset == 0 && t > 1) 	{ onset  = t-dt
							                  vonset = v2 }
			below     = 0	
			if (vhalf > v) {below = 1}
			if (below == 0 && below_old == 1 && upstroke == 0)   {upstroke = t}
			if (below == 1 && below_old == 0 && downstroke == 0) {downstroke = t}

			halfwidth = downstroke - upstroke
			below_old = below
}

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