The electroretinogram and visual evoked potential of freely moving rats.

The vascularised rat retina could be one of the most useful experimental objects in visual neuroscience to understand human visual physiological and pathological processes. We report here on a new method of implantation for studying the visual system of freely moving rats that provides a rat model for simultaneous recording at corneal and cortical level and is stable enough to record for months. We implanted light emitting diodes onto the skull behind the eyeball to stimulate the eye with flashes and to light adapt the retina with constant light levels. A multistrand, stainless steel, flexible fine wire electrode placed on the eyeball was used for electroretinogram recording and screw electrodes (left/right visual and parietal cortical) were used to record the visual evoked potential and the electroencephalogram. In the present report we focus on the new method of implantation for recording the corneal flash electroretinogram of normal, freely moving rats simultaneously with the visual evoked cortical potential showing examples in various visual experiments. We also introduce a program for retinogram and visual evoked potential analysis, which defines various measures (latencies, areas, amplitudes, and durations) and draw attention to the benefits of this method for those involved in visual, functional genomic, pharmacological, and human ophthalmologic research.

Sleep modifies retinal ganglion cell responses in the normal rat.

Recordings were obtained from the visual system of rats as they cycled normally between waking (W), slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Responses to flashes delivered by a light-emitting diode attached permanently to the skull were recorded through electrodes implanted on the cornea, in the chiasm, and on the cortex. The chiasm response reveals the temporal order in which the activated ganglion cell population exits the eyeball; as reported, this triphasic event is invariably short in latency (5--10 ms) and around 300 ms in duration, called the histogram. Here we describe the differences in the histograms recorded during W, SWS, and REM. SWS histograms are always larger than W histograms, and an REM histogram can resemble either. In other words, the optic nerve response to a given stimulus is labile; its configuration depends on whether the rat is asleep or awake. We link this physiological information with the anatomical fact that the brain dorsal raphe region, which is known to have a sleep regulatory role, sends fibers to the rat retina and receives fibers from it. At the cortical electrode, the visual cortical response amplitudes also vary, being largest during SWS. This well known phenomenon often is explained by changes taking place at the thalamic level. However, in the rat, the labile cortical response covaries with the labile optic nerve response, which suggests the cortical response enhancement during SWS is determined more by what happens in the retina than by what happens in the thalamus.

Temporal distribution of the ganglion cell volleys in the normal rat optic nerve.

We describe experiments on behaving rats with electrodes implanted on the cornea, in the optic chiasm, and on the visual cortex; in addition, two red light-emitting diodes (LED) are permanently attached to the skull over the left eye. Recordings timelocked to the LED flashes reveal both the local events at each electrode site and the orderly transfer of visual information from retina to cortex. The major finding is that every stimulus, regardless of its luminance, duration, or the state of retinal light adaptation, elicits an optic nerve volley with a latency of about 10 ms and a duration of about 300 ms. This phenomenon has not been reported previously, so far as we are aware. We conclude that the retina, which originates from the forebrain of the developing embryo, behaves like a typical brain structure: it translates, within a few hundred milliseconds, the chemical information in each pattern of bleached photoreceptors into a corresponding pattern of ganglion cell neuronal information that leaves via the optic nerve. The attributes of each rat ganglion cell appear to include whether the retinal neuropile calls on it to leave after a stimulus and, if so when, within a 300-ms poststimulus epoch. The resulting retinal analysis of the scene, on arrival at the cortical level, is presumed to participate importantly in the creation of visual perceptual experiences.

Slow wave sleep is accompanied by release of certain amino acids in the thalamus of cats.

To determine whether EEG synchronization in sleep has a metabolic equivalent, we investigated state-dependent changes in extracellular concentrations of amino acids. In vivo microdialysis studies were performed in the ventroposterolateral (VPL) nuclei of the thalamus of cats during natural slow wave sleep (SWS), waking (W) and carbachol-induced paradoxical sleep (PS) like episodes. About two-fold increases in aspartate, glutamate, asparagine, glycine, alanine and gamma-aminobutyric acid (GABA) were observed in SWS compared with control samples collected in W, but serine increased to 487 +/- 211%. In the PS-like state, glutamine increased and GABA decreased. These results suggest changes in intracellular processes reflected by amino acid release in the thalamus, specific to slow wave generation in EEG during natural sleep.

Blockade of thalamic GABAB receptors decreases EEG synchronization.

The gamma-aminobutyric acid (GABA)B receptor antagonists 2-OH-saclofen and CGP 35348 were injected in the thalamus of freely moving cats via a microdialysis probe while recording the sleep-walking cycle. The results obtained with the two antagonists were similar: wakefulness and the total sleep time were not affected by the blockade of GABAB receptors, but deep slow wave sleep and the mean power of slow waves (< 10 Hz) were decreased, while light slow wave sleep was increased. These data suggest an involvement of thalamic GABAB receptors in the regulation of EEG slow waves.