GenNet: A Platform for Hybrid Network Experiments

We describe General Network (GenNet), a software plugin for the real time experimental interface (RTXI) dynamic clamp system that allows for straightforward and flexible implementation of hybrid network experiments. This extension to RTXI allows for hybrid networks that contain an arbitrary number of simulated and real neurons, significantly improving upon previous solutions that were limited, particularly by the number of cells supported. The benefits of this system include the ability to rapidly and easily set up and perform scalable experiments with hybrid networks and the ability to scan through ranges of parameters. We present instructions for installing, running and using GenNet for hybrid network experiments and provide several example uses of the system

The Mechanism of Abrupt Transition between Theta and Hyper-Excitable Spiking Activity in Medial Entorhinal Cortex Layer II Stellate Cells

Recent studies have shown that stellate cells (SCs) of the medial entorhinal cortex become hyper-excitable in animal models of temporal lobe epilepsy. These studies have also demonstrated the existence of recurrent connections among SCs, reduced levels of recurrent inhibition in epileptic networks as compared to control ones, and comparable levels of recurrent excitation among SCs in both network types. In this work, we investigate the biophysical and dynamic mechanism of generation of the fast time scale corresponding to hyper-excitable firing and the transition between theta and fast firing frequency activity in SCs. We show that recurrently connected minimal networks of SCs exhibit abrupt, threshold-like transition between theta and hyper-excitable firing frequencies as the result of small changes in the maximal synaptic (AMPAergic) conductance. The threshold required for this transition is modulated by synaptic inhibition. Similar abrupt transition between firing frequency regimes can be observed in single, self-coupled SCs, which represent a network of recurrently coupled neurons synchronized in phase, but not in synaptically isolated SCs as the result of changes in the levels of the tonic drive. Using dynamical systems tools (phase-space analysis), we explain the dynamic mechanism underlying the genesis of the fast time scale and the abrupt transition between firing frequency regimes, their dependence on the intrinsic SC's currents and synaptic excitation. This abrupt transition is mechanistically different from others observed in similar networks with different cell types. Most notably, there is no bistability involved. ‘In vitro’ experiments using single SCs self-coupled with dynamic clamp show the abrupt transition between firing frequency regimes, and demonstrate that our theoretical predictions are not an artifact of the model. In addition, these experiments show that high-frequency firing is burst-like with a duration modulated by an M-current

The point process model predicts changes of synaptic coupling strengths due to pharmacological conditions.

<p><b>A</b>, Exemplary spike trains from the control condition (left) and after application of CsCl, which blocks the h-current in all neurons (right). The pyloric rhythm is maintained in both conditions. <b>B</b>, Inferred coupling strengths for the control (left) and CsCl condition (right). All coupling strengths (self- and cross-couplings) become stronger, that is, more inhibitory. The mean of all eight coupling strengths (thick line, all except PY-to-PD) increases significantly between the control and CsCl condition. The nonexistent PY-to-PD coupling remains the weakest coupling in both conditions (blue line). <b>C</b>, Relative change of (signed) coupling strengths between the two conditions. Same data as in <b>B</b>, but expressed as the change of coupling strength relative to the control condition. All couplings become more inhibitory with a mean relative change of 450% (left). The relative change of the PY-to-PD coupling has the opposite sign (right). <b>D</b>, Exemplary spike trains from the control condition (left) and after application of PTX, blocking glutamatergic synaptic transmission (right). The pyloric rhythm is qualitatively maintained in both conditions. <b>E</b>, Inferred coupling strengths for the control (left) and PTX condition (right). All coupling strengths become weaker, that is, less inhibitory. The mean of all five existing cross-couplings (thick line) decreases significantly between the control and PTX condition. The nonexistent PY-to-PD coupling remains the weakest coupling in both conditions (blue line). <b>F</b>, Relative change of coupling strengths between the two conditions. Same data as in <b>E</b>, but expressed as the change of coupling strength relative to the control condition. All couplings become weaker with a mean relative change of −85% (left). The relative change of the PY-to-PD coupling has the opposite sign (right). <b>G</b>, Spike trains generated from the model of the PTX data set with various network constraints. Spike trains obtained from the PTX condition were used for five seconds, afterward spikes were simulated using either the full model (left top), a model with the PY-to-PD link forced to zero (right top), a network structure allowing only for non-glutamatergic synapses (left bottom) or a model with no cross-interactions (right bottom). All models except the last one produce spike trains comparable to the real data. The model without any cross-interactions show burst-like and tonic activity but neurons do not fire with a fixed relative phase.</p