Presynaptic GABAB receptors underlie the antiepileptic effect of low-frequency electrical stimulation in the 4-aminopyridine model of epilepsy in brain slices of young rats.

Low-frequency electrical stimulation (LFES) of the brain is one of the promising methods for helping patients with pharmacoresistant epilepsy. However, the mechanism of the antiepileptic effect of LFES is still unclear. We applied electrophysiological and pharmacological tools and mathematical modeling to investigate it. Using the 4-aminopyridine (4-AP) model of epileptiform activity in juvenile rat brain slices, we found that LFES increased the interval between ictal discharges (IDs) in the entorhinal cortex. The blockade of GABAA, GABAB, AMPA, or NMDA synaptic receptors strongly affected the characteristics of epileptiform discharges in slices. However, only under the blockade of GABAB receptors, LFES becomes entirely ineffective, indicating that the activation of GABAB receptors underlies the main LFES antiepileptic effect. Further experiments allowed us to suggest that LFES activates mostly presynaptic GABAB receptors, which decrease the probability of glutamate release. In line with this hypothesis is the following data: 1) LFES reduces the short-term synaptic depression of excitatory postsynaptic currents similar to the agonist of GABAB receptors SKF-97541; 2) the blockade of excitatory amino acid transporters diminishes the antiepileptic effect of LFES; 3) modeling of the effects of LFES on the probability of glutamate release with a previously proposed mathematical model of epileptiform activity Epileptor-2 also shows the increase of the interval between IDs. Our findings point out a crucial role of presynaptic GABAB receptors in the antiepileptic effect of LFES in the 4-AP model in juvenile rat brain slices.

Acute Changes in Electrophysiological Properties of Cortical Regular-Spiking Cells Following Seizures in a Rat Lithium-Pilocarpine Model.

Profound alterations in both the synaptic and intrinsic membrane properties of neurons that increase the neuronal network excitability are found in epileptic tissue. However, there are still uncertainties regarding the kind of changes in the intrinsic membrane properties occurring during epileptogenesis. Epileptogenesis is typically triggered by the initial brain-damaging insult, and status epilepticus (SE) is one of such insults. In the present study, we explored the acute changes in the intrinsic membrane properties of pyramidal cells one day after SE in a rat lithium-pilocarpine model. Using whole-cell patch-clamp recording and the dynamic-clamp technique, we investigated the properties of regular-spiking neurons in the entorhinal cortex (EC) and the medial prefrontal cortex (PFC), two areas differentially affected by SE. We found that one day after SE: (1) the intrinsic membrane properties of EC neurons are significantly altered, while the properties of PFC neurons are mostly unchanged; (2) the input resistance and membrane time constant of regular-spiking neurons are reduced due to enhanced leak current; (3) the active membrane properties of neurons are mostly unaffected; and (4) changes in the passive membrane properties diminish the intrinsic neuronal excitability. Therefore, our results suggest that the acute changes in the intrinsic membrane properties of entorhinal neurons following pilocarpine-induced SE do not contribute to network hyperexcitability. In contrast, at the early stage of epileptogenesis, protective homeostatic plasticity of intrinsic membrane properties is observed in the EC; it reduces the neuronal excitability in response to increased network excitability.

A mathematical model of color and orientation processing in V1.

Orientation processing in the primary visual cortex (V1) has been experimentally investigated in detail and reproduced in models, while color processing remains unclear. Thus, we have constructed a mathematical model of color and orientation processing in V1. The model is mainly based on the following experimental evidence concerning color blobs: A blob contains overlapping neuronal patches activated by different hues, so that each blob represents a full gamut of hue and might be structured with a loop (Xiao et al. in NeuroImage 35:771-786, 2007). The proposed model describes a set of orientation hypercolumns and color blobs, in which color and orientation preferences are represented by the poloidal and toroidal angles of a torus, correspondingly. The model consists of color-insensitive (CI) and color-sensitive (CS) neuronal populations, which are described by a firing-rate model. The set of CI neurons is described by the classical ring model (Ben-Yishai et al. in Proc Natl Acad Sci USA 92:3844-3848, 1995) with recurrent connections in the orientation space; similarly, the set of CS neurons is described in the color space and also receives input from CI neurons of the same orientation preference. The model predictions are as follows: (1) responses to oriented color stimuli are significantly stronger than those to non-oriented color stimuli; (2) the activity of CS neurons in total is higher than that of CI neurons; (3) a random color can be illusorily perceived in the case of gray oriented stimulus; (4) in response to two-color stimulus in the marginal phase, the network chooses either one of the colors or the intermediate color; (5) input to a blob has rather continual representation of a hue than discrete one (with two narrowly tuned opponent signals).

Electrical capacitance of lipid bilayer membranes of hydrogenated egg lecithin at the temperature phase transition.

Electrical capacitance of the planar bilayer lipid membrane (BLM) formed from hydrogenated egg lecithin (HEL) has been studied during many passages through the phase transition temperature. In contrast to the BLM from individual synthetic phospholipids, membranes from HEL did not demonstrate any capacitance change at the phase transition temperature maximum, as measured by differential scanning calorimeter at 52 degrees C. Instead, two temperatures have been discerned by capacitance records: thickening at 42-43 degrees C and thinning at 57-59 degrees C. The first temperature region is close to the transition temperature of dipalmitoyllecithin, whereas the second is close to that of distearoyllecithin, two main components of the HEL. It was suggested that capacitance measurements were able to reveal a phase separation in the BLM from HEL which was not detected by differential scanning calorimetry. The phase transition of the BLM from the liquid crystal state to the gel state is followed by thickening of the bilayer structure, partly due to a gauche- trans transition of lipid molecules but mainly due to redistribution of the solvent n-decane.