Mammalian Brain As a Network of Networks

Acknowledgements AZ, SG and AL acknowledge support from the Russian Science Foundation (16-12-00077). Authors thank T. Kuznetsova for Fig. 6.Peer reviewedPublisher PD

Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes

Abstract: Astrocytes are involved in maintenance of synaptic microenvironment by glutamate uptake and K+ clearance. These processes are associated with net charge transfer across the membrane and therefore can be recorded as glutamate transporter (IGluT) and K+ (IK) currents. It has been previously shown that the blockade of IK with BaCl2 enhances the IGluT. Here we show that activity-dependent facilitation (5 stimuli at 50 Hz) of IGluT was not significantly different in BaCl2 compared to facilitation of IGluT isolated by post-hoc subtraction of IK. Nevertheless, BaCl2 abolished the activity-dependent prolongation of τdecay, which was observed for IGluT isolated by post-hoc subtraction of IK. This finding suggests that activity-dependent accumulation of extracellular K+ ([K+]o) causes astrocytic depolarization, which is responsible for the increase in τdecay of IGluT. The blockade of inward rectifying K+ channels (Kir) with BaCl2 makes astrocytic membrane potential insensitive to [K+]o elevation and thus abolishes this increase. Blockade of IGluT with glutamate transporter blocker, DL-threo-β- benzyloxyaspartic acid (TBOA) did not significantly affect the amplitude of IK but decreased its τdecay. However, activity dependent facilitations of both amplitude and τdecay of IK were larger in TBOA, than in the control conditions. We suggest that activity-dependent accumulation of extracellular glutamate can enhance release of K+. Thus activity-dependent changes in [K+]o can affect glutamate dwell-time in the synaptic cleft, and vice versa, extracellular glutamate accumulation can affect [K+]o time-course. Our finding is important for understanding of the astrocytic mechanisms in glutamate excitotoxicity and in diseases related to disruption of K+ homeostasis (e.g. stroke, migraine, and epilepsy)

Recording of excitatory postsynaptic potentials after tonic stimulation from hybrid neural circuit

Recordings of excitatory postsynaptic potentials of hippocampal living neurons in acute hippocampal brain slices after tonic pulse stimulation from hybrid neural circuit

Optoelectronic system for brain neuronal network stimulation.

We propose an optoelectronic system for stimulation of living neurons. The system consists of an electronic circuit based on the FitzHugh-Nagumo model, an optical fiber, and a photoelectrical converter. We used this system for electrical stimulation of hippocampal living neurons in acute hippocampal brain slices (350-μm thick) obtained from a 20-28 days old C57BL/6 mouse or a Wistar rat. The main advantage of our system over other similar stimulators is that it contains an optical fiber for signal transmission instead of metallic wires. The fiber is placed between the electronic circuit and stimulated neurons and provides galvanic isolation from external electrical and magnetic fields. The use of the optical fiber allows avoiding electromagnetic noise and current flows which could affect metallic wires. Furthermore, it gives us the possibility to simulate "synaptic plasticity" by adaptive signal transfer through optical fiber. The proposed optoelectronic system (hybrid neural circuit) provides a very high efficiency in stimulating hippocampus neurons and can be used for restoring brain activity in particular regions or replacing brain parts (neuroprosthetics) damaged due to a trauma or neurodegenerative diseases

Oscillograms of FHN neuron (curve 1) and amplified photodiode (curve 2) voltages.

<p>Oscillograms of FHN neuron (curve 1) and amplified photodiode (curve 2) voltages.</p

Optoelectronic system for brain neuronal network stimulation - Fig 5

<p>Experimental scheme with electrodes location for recording (a) population spike and (b) excitatory postsynaptic potentials, and (c,d) corresponding neuron responses. Registration electrode detect (a) evoked population spike from pyramidal neurons somas and (b) excitatory postsynaptic potentials from dendrites of pyramidal neurons during electrical stimulation of Shaffer collaterals.</p

Scheme of our biological experiment with hybrid neural circuit.

<p>Scheme of our biological experiment with hybrid neural circuit.</p

Optoelectronic system for brain neuronal network stimulation - Fig 6

<p>Recording of EPSPs after tonic stimulation from hybrid neural circuit with (a) 12-Hz 1-V pulses and (b) 20-Hz 2.5-V pulses.</p

Scheme of the hybrid neural circuit.

<p>Scheme of the hybrid neural circuit.</p