Synaptic working memory (WM) with astrocytic signaling: Synapse and network model.

A Sketch of the transmission dynamics at tripartite glutamatergic synapses, as determined by the components of presynaptic STP, and its modulation by the astrocytic enzyme ATX [43] and the postsynaptic protein PRG1 [42] via lysophosphatidic acid (LPA). Presynaptic STP influences synaptic transmission via glutamate availability (blue) and calcium-binding (green) at the presynaptic terminal. The astrocytic and postsynaptic components modulate presynaptic calcium-binding rates by increasing the concentration of LPA in the synaptic cleft, which allows more LPA in the synaptic cleft (orange) to bind to the presynaptic LPA2 receptors. Postsynaptic calcium increases LPA concentrations in the cleft by inhibiting the postsynaptic protein PRG1 (via CaM) that usually takes up newly synthesized LPA from the cleft. Astrocytic, ATX-mediated synthesis of LPA is amplified in a activity-dependent way, since some of the synaptically transmitted glutamate binds to astrocytic receptors that increase ATX activity. Implications of elevated calcium-binding due to LPA signaling for paired-pulse-ratio are shown in Fig B in S1 Text. B Sketch of the synapse model that captures the transmission dynamics shown in (A). The dynamics of the synaptic variables x (neurotransmitter availability), y (presynaptic calcium binding), and ℓ (presynaptic LPA binding) are determined by the STP parameters U, τD and τF and the additional astrocytic signaling parameters ΔU (maximal LPA-mediated increase of U), M (activity-dependent increase of ℓ) and τL (decay timescale of ℓ). The equations of the synapse model (Eqs 1, 2, 4 and 5) and the dynamics of each variable are described in Models and Methods. (C Sketch of the spiking network model of synaptic WM (architecture as in Mongillo et al. [5]). The network consists of two excitatory populations and one global inhibitory population. Each population consists of sparsely and randomly connected LIF neurons. During the WM protocol, all neurons receive an excitatory baseline input with Gaussian white noise. When the WM cue is presented, the neurons of the excitatory selective population receive an additional external input Icue. All except excitatory-to-excitatory (E-E) connections have fixed synaptic weights. All E-E connections underlie either only STP (STP networks) or STP with astrocytic modulation by the LPA-mechanism as sketched in A and B (STP+LPA spiking network). D Sketch of the rate network model of synaptic WM. The rate network consists of one excitatory population that is described by a single population firing rate. The recurrent excitatory connections underlie either only STP or STP with astrocytic modulation (LPA-mechanism) as sketched in A and B. We refer to these networks as STP rate networks and STP+LPA rate networks, respectively. During the entire WM protocol, the excitatory population receives a constant baseline input current with Gaussian white noise. This input is inhibitory since it represents the combined effect of global inhibitory and inputs from surrounding (non-selective) excitatory populations. During the cue presentation, it receives an additional excitatory input current Icue.