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]
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;
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kadist.mod *
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kca.mod *
kdrca1.mod *
kmb.mod *
ltpltd.mod *
naxn.mod *
netstims.mod *
Revised 12/15/2000 in light of a personal communication 
from Misha Tsodyks that u is incremented _before_ x is 
converted to y--a point that was not clear in the paper.
If u is incremented _after_ x is converted to y, then 
the first synaptic activation after a long interval of 
silence will produce smaller and smaller postsynaptic 
effect as the length of the silent interval increases, 
eventually becoming vanishingly small.

Implementation of a model of short-term facilitation and depression 
based on the kinetics described in
  Tsodyks et al.
  Synchrony generation in recurrent networks 
  with frequency-dependent synapses
  Journal of Neuroscience 20:RC50:1-5, 2000.
Their mechanism represented synapses as current sources.
The mechanism implemented here uses a conductance change instead.

The basic scheme is

x -------> y    Instantaneous, spike triggered.
                Increment is u*x (see discussion of u below).
                x == fraction of "synaptic resources" that have 
                     "recovered" (fraction of xmtr pool that is 
                     ready for release, or fraction of postsynaptic 
                     channels that are ready to be opened, or some 
                     joint function of these two factors)
                y == fraction of "synaptic resources" that are in the 
                     "active state."  This is proportional to the 
                     number of channels that are open, or the 
                     fraction of max synaptic current that is 
                     being delivered. 
y -------> z    z == fraction of "synaptic resources" that are 
                     in the "inactive state"

z -------> x

where x + y + z = 1

The active state y is multiplied by a synaptic weight to compute
the actual synaptic conductance (or current, in the original form 
of the model).

In addition, there is a "facilition" term u that 
governs the fraction of x that is converted to y 
on each synaptic activation.

  -------> u    Instantaneous, spike triggered, 
                happens _BEFORE_ x is converted to y.
                Increment is U*(1-u) where U and u both 
                lie in the range 0 - 1.
u ------->      decay of facilitation

This implementation for NEURON offers the user a parameter 
u0 that has a default value of 0 but can be used to specify 
a nonzero initial value for u.

When tau_facil = 0, u is supposed to equal U.

Note that the synaptic conductance in this mechanism 
has the same kinetics as y, i.e. decays with time 
constant tau_1.

This mechanism can receive multiple streams of 
synaptic input via NetCon objects.  
Each stream keeps track of its own 
weight and activation history.

The printf() statements are for testing purposes only.

11 April 2019, modified to take into account exc syn from A. Scimemi (RM) tau_rec=10 tau_1=4.5

	RANGE e, i
	RANGE tau_1, tau_rec, tau_facil, U, u0

	(nA) = (nanoamp)
	(mV) = (millivolt)
	(umho) = (micromho)

	: e = -90 mV for inhibitory synapses,
	:     0 mV for excitatory
	e = 0	(mV)
	: tau_1 was the same for inhibitory and excitatory synapses
	: in the models used by T et al.
	tau_1 = 3 (ms) < 1e-9, 1e9 > : original value 3
	: tau_rec = 100 ms for inhibitory synapses,
	:           800 ms for excitatory
	tau_rec = 20 (ms) < 1e-9, 1e9 >  : 50 for night 
	: tau_facil = 1000 ms for inhibitory synapses,
	:             0 ms for excitatory
	tau_facil = 1000 (ms) < 0, 1e9 >
	: U = 0.04 for inhibitory synapses, 
	:     0.5 for excitatory
	: the (1) is needed for the < 0, 1 > to be effective
	:   in limiting the values of U and u0
	U = 0.2 (1) < 0, 1 >
	: initial value for the "facilitation variable"
	u0 = 0 (1) < 0, 1 >

	v (mV)
	i (nA)

	g (umho)


	SOLVE state METHOD cnexp
	i = g*(v - e)

	g' = -g/tau_1

NET_RECEIVE(weight (umho), y, z, u, tsyn (ms)) {
: these are in NET_RECEIVE to be per-stream
	y = 0
	z = 0
:	u = 0
	u = u0
	tsyn = t
: this header will appear once per stream
: printf("t\t t-tsyn\t y\t z\t u\t newu\t g\t dg\t newg\t newy\n")

	: first calculate z at event-
	:   based on prior y and z
	z = z*exp(-(t - tsyn)/tau_rec)
	z = z + ( y*(exp(-(t - tsyn)/tau_1) - exp(-(t - tsyn)/tau_rec)) / ((tau_1/tau_rec)-1) )
	: now calc y at event-
	y = y*exp(-(t - tsyn)/tau_1)

	x = 1-y-z

	: calc u at event--
	if (tau_facil > 0) {
		u = u*exp(-(t - tsyn)/tau_facil)
	} else {
		u = U

: printf("%g\t%g\t%g\t%g\t%g", t, t-tsyn, y, z, u)

	if (tau_facil > 0) {
		state_discontinuity(u, u + U*(1-u))

: printf("\t%g\t%g\t%g", u, g, weight*x*u)

	state_discontinuity(g, g + weight*x*u)
	state_discontinuity(y, y + x*u)

	tsyn = t

: printf("\t%g\t%g\n", g, y)

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