CA1 pyramidal neurons: effects of Alzheimer (Culmone and Migliore 2012)

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Accession:144976
The model predicts possible therapeutic treatments of Alzheimers's Disease in terms of pharmacological manipulations of channels' kinetic and activation properties. The results suggest how and which mechanism can be targeted by a drug to restore the original firing conditions. The simulations reproduce somatic membrane potential in control conditions, when 90% of membrane is affected by AD (Fig.4A of the paper), and after treatment (Fig.4B of the paper).
Reference:
1 . Culmone V, Migliore M (2012) Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments. Front Comput Neurosci 6:52 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Channel/Receptor; Dendrite;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I A; I K; I h;
Gap Junctions:
Receptor(s): AMPA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu]; Culmone, Viviana [viviana.abigail at hotmail.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; I Na,t; I A; I K; I h;
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alzheimer
readme.html
distr.mod *
h.mod *
kadist.mod
kaprox.mod *
kdrca1.mod *
na3n.mod *
naxn.mod *
netstims.mod *
10sim.ses
fixnseg.hoc *
geo5038804.hoc
membrane_potential.hoc
mosinit.hoc
screenshot.png
                            
: $Id: netstim.mod,v 1.1.1.1 2001/01/01 20:30:37 hines Exp $
: modified in such a way that the first event will never be before start
: M.Migliore Dec.2001
: modified in such a way to have the first event at start
: M.Migliore Sep. 2003

NEURON	{ 
  POINT_PROCESS NetStims
  RANGE y
  RANGE interval, number, start
  RANGE noise
}

PARAMETER {
	interval	= 10 (ms) <1e-9,1e9>: time between spikes (msec)
	number	= 10 <0,1e9>	: number of spikes
	start		= 50 (ms)	: start of first spike
	noise		= 0 <0,1>	: amount of randomeaness (0.0 - 1.0)
}

ASSIGNED {
	y
	event (ms)
	on
	end (ms)
}

PROCEDURE seed(x) {
	set_seed(x)
}

INITIAL {
	on = 0
	y = 0
	if (noise < 0) {
		noise = 0
	}
	if (noise > 1) {
		noise = 1
	}
	if (start >= 0 && number > 0) {
	: first spike occurs at start
		event = start
		net_send(event, 3)
	}
}	

PROCEDURE init_sequence(t(ms)) {
	if (number > 0) {
		on = 1
		event = t
		end = t + 1e-6 + invl(interval)*(number-1)
	}
}

FUNCTION invl(mean (ms)) (ms) {
	if (mean <= 0.) {
		mean = .01 (ms) : I would worry if it were 0.
	}
	if (noise == 0) {
		invl = mean
	}else{
		invl = (1. - noise)*mean + noise*mean*exprand(1)
	}
}

PROCEDURE event_time() {
	if (number > 0) {
		event = event + invl(interval)
	}
	if (event > end) {
		on = 0
	}
}

NET_RECEIVE (w) {
	if (flag == 0) { : external event
		if (w > 0 && on == 0) { : turn on spike sequence
			init_sequence(t)
			net_send(0, 1)
		}else if (w < 0 && on == 1) { : turn off spiking
			on = 0
		}
	}
	if (flag == 3) { : from INITIAL
		if (on == 0) {
			init_sequence(t)
			net_send(0, 1)
		}
	}
	if (flag == 1 && on == 1) {
		y = 2
		net_event(t)
		event_time()
		if (on == 1) {
			net_send(event - t, 1)
		}
		net_send(.1, 2)
	}
	if (flag == 2) {
		y = 0
	}
}

COMMENT
Presynaptic spike generator
---------------------------

This mechanism has been written to be able to use synapses in a single
neuron receiving various types of presynaptic trains.  This is a "fake"
presynaptic compartment containing a spike generator.  The trains
of spikes can be either periodic or noisy (Poisson-distributed)

Parameters;
   noise: 	between 0 (no noise-periodic) and 1 (fully noisy)
   interval: 	mean time between spikes (ms)
   number: 	mean number of spikes

Written by Z. Mainen, modified by A. Destexhe, The Salk Institute

Modified by Michael Hines for use with CVode
The intrinsic bursting parameters have been removed since
generators can stimulate other generators to create complicated bursting
patterns with independent statistics (see below)

Modified by Michael Hines to use logical event style with NET_RECEIVE
This stimulator can also be triggered by an input event.
If the stimulator is in the on=0 state and receives a positive weight
event, then the stimulator changes to the on=1 state and goes through
its entire spike sequence before changing to the on=0 state. During
that time it ignores any positive weight events. If, in the on=1 state,
the stimulator receives a negative weight event, the stimulator will
change to the off state. In the off state, it will ignore negative weight
events. A change to the on state immediately fires the first spike of
its sequence.

ENDCOMMENT