Circadian rhythmicity shapes astrocyte morphology and neuronal function in CA1 (McCauley et al 2020)

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Most animal species operate according to a 24-hour period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN modulates hippocampal-dependent memory, but the molecular and cellular mechanisms that account for this effect remain largely unknown. In McCauley et al. 2020 [1], we identify cell-type specific structural and functional changes that occur with circadian rhythmicity in neurons and astrocytes in hippocampal area CA1. Pyramidal neurons change the surface expression of NMDA receptors. Astrocytes change their proximity clustered excitatory synaptic inputs, ultimately shaping hippocampal-dependent learning in vivo. We identify to synapses. Together, these phenomena alter glutamate clearance, receptor activation and integration of temporally corticosterone as a key contributor to changes in synaptic strength. These findings highlight important mechanisms through which neurons and astrocytes modify the molecular composition and structure of the synaptic environment, contribute to the local storage of information in the hippocampus and alter the temporal dynamics of cognitive processing. [1] "Circadian modulation of neurons and astrocytes controls synaptic plasticity in hippocampal area CA1" by J.P. McCauley, M.A. Petroccione, L.Y. D’Brant, G.C. Todd, N. Affinnih, J.J. Wisnoski, S. Zahid, S. Shree, A.A. Sousa, R.M. De Guzman, R. Migliore, A. Brazhe, R.D. Leapman, A. Khmaladze, A. Semyanov, D.G. Zuloaga, M. Migliore and A. Scimemi. Cell Reports (2020),
1 . McCauley JP, Petroccione MA, D'Brant LY, Todd GC, Affinnih N, Wisnoski JJ, Zahid S, Shree S, Sousa AA, De Guzman RM, Migliore R, Brazhe A, Leapman RD, Khmaladze A, Semyanov A, Zuloaga DG, Migliore M, Scimemi A (2020) Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1. Cell Rep 33:108255 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Channel/Receptor;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Astrocyte;
Channel(s): I A; I h; I M; I K; I K,Ca; Ca pump; I Calcium; I CAN; I Na,t;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Integration; Synaptic Plasticity; Detailed Neuronal Models;
Implementer(s): Migliore, Rosanna [rosanna.migliore at]; Migliore, Michele [Michele.Migliore at];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; Ca pump; Glutamate;
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can2.mod *
cat.mod *
h.mod *
kadist.mod *
kaprox.mod *
kca.mod *
kdrca1.mod *
kmb.mod *
ltpltd.mod *
naxn.mod *
netstims.mod *
TITLE simple NMDA receptors

: Modified from the original AMPA.mod, M.Migliore Jan 2003
: A weight of 0.0035 gives a peak conductance of 1nS in 0Mg


	Simple model for glutamate AMPA receptors


    Whole-cell recorded postsynaptic currents mediated by AMPA/Kainate
    receptors (Xiang et al., J. Neurophysiol. 71: 2552-2556, 1994) were used
    to estimate the parameters of the present model; the fit was performed
    using a simplex algorithm (see Destexhe et al., J. Computational Neurosci.
    1: 195-230, 1994).


    The simplified model was obtained from a detailed synaptic model that 
    included the release of transmitter in adjacent terminals, its lateral 
    diffusion and uptake, and its binding on postsynaptic receptors (Destexhe
    and Sejnowski, 1995).  Short pulses of transmitter with first-order
    kinetics were found to be the best fast alternative to represent the more
    detailed models.


    The first-order model can be solved analytically, leading to a very fast
    mechanism for simulating synapses, since no differential equation must be
    solved (see references below).


   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  An efficient method for
   computing synaptic conductances based on a kinetic model of receptor binding
   Neural Computation 6: 10-14, 1994.  

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Synthesis of models for
   excitable membranes, synaptic transmission and neuromodulation using a 
   common kinetic formalism, Journal of Computational Neuroscience 1: 
   195-230, 1994.


	RANGE R, g, mg
	GLOBAL Cdur, Alpha, Beta, Erev, Rinf, Rtau
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(umho) = (micromho)
	(mM) = (milli/liter)


	Cdur	= 1		(ms)	: transmitter duration (rising phase)
	Alpha	= 0.35		(/ms)	: forward (binding) rate 0.35
	Beta	= 0.005		(/ms)	: backward (unbinding) rate 0.035
:	Alpha	= 0.072		(/ms)	: forward (binding) rate
:	Beta	= 0.0066		(/ms)	: backward (unbinding) rate
	Erev	= 0	(mV)		: reversal potential
	mg	= 1    (mM)		: external magnesium concentration

	v		(mV)		: postsynaptic voltage
	i 		(nA)		: current = g*(v - Erev)
	g 		(umho)		: conductance
	Rinf				: steady state channels open
	Rtau		(ms)		: time constant of channel binding

STATE {Ron Roff}

	Rinf = Alpha / (Alpha + Beta)
	Rtau = 1 / (Alpha + Beta)
	synon = 0

	SOLVE release METHOD cnexp
	g = mgblock(v)*(Ron + Roff)*1(umho)
	i = g*(v - Erev)		

DERIVATIVE release {
	Ron' = (synon*Rinf - Ron)/Rtau
	Roff' = -Beta*Roff

: following supports both saturation from single input and
: summation from multiple inputs
: if spike occurs during CDur then new off time is t + CDur
: ie. transmitter concatenates but does not summate
: Note: automatic initialization of all reference args to 0 except first

FUNCTION mgblock(v(mV)) {
	FROM -140 TO 80 WITH 1000

	: from Jahr & Stevens

	mgblock = 1 / (1 + exp(0.062 (/mV) * -v) * (mg / 3.57 (mM)))

NET_RECEIVE(weight, on, nspike, r0, t0 (ms)) {
	: flag is an implicit argument of NET_RECEIVE and  normally 0
        if (flag == 0) { : a spike, so turn on if not already in a Cdur pulse
		nspike = nspike + 1
		if (!on) {
			r0 = r0*exp(-Beta*(t - t0))
			t0 = t
			on = 1
			synon = synon + weight
			state_discontinuity(Ron, Ron + r0)
			state_discontinuity(Roff, Roff - r0)
		: come again in Cdur with flag = current value of nspike
		net_send(Cdur, nspike)
	if (flag == nspike) { : if this associated with last spike then turn off
		r0 = weight*Rinf + (r0 - weight*Rinf)*exp(-(t - t0)/Rtau)
		t0 = t
		synon = synon - weight
		state_discontinuity(Ron, Ron - r0)
		state_discontinuity(Roff, Roff + r0)
		on = 0