Reorganization of neural circuits in area 17 of the cat following retinal lesions in adolescent kittens

Abstract presented at the Physiological Society Meeting, Aberdeen, 200

Laminar differences in plasticity in striate cortex of cats

We have previously reported to the Society that in cats in which monocular retinal lesions were made in adulthood or adolescence cells in the lesion projection zone (LPZ) of area 17 recovered sensitivity to photic stimuli but the receptive fields (RFs) were now ectopic, i.e. outside the lesion (Burke et al. 2000). When the lesions were made in adult cats (AL), stimuli presented via the lesioned eye gave lower peak discharge rates and lower cut-off velocities than those presented via the non-lesioned eye. By contrast, in kitten-lesioned cats (KL) the cut-off velocities and the peak discharge rates were similar for stimuli presented via the lesioned and the non-lesioned eye. There was, however, a difference in the time from lesion to experiment between the AL and KL groups, 2-24 weeks vs. 28-68 weeks. It was, therefore, important to see if this factor could be responsible for the neural effects. Ectopic RFs are believed to be mediated via axon collaterals of pyramidal cells interconnecting mainly in laminae 2 and 3. We, therefore, also investigated the location of the LPZ neurones (supragranular (SG) - laminae 1-3: granular/ infragranular (G/I) - laminae 4-6). In addition to the two groups already described (AL 4 cats; KL 5 cats) we prepared a third group in which the lesion was made in the adult cat but the cat then survived 3.5-4.5 years (AL/L 3 cats). Retinal lesions 8-12 deg in diameter were made in cats anaesthetized with xylazine (3 mg kg-1) and ketamine (30 mg kg-1). Single neurones in area 17 were studied in cats anaesthetized with 0.5-0.7 % halothane in 67/33 N2O/O2, given gallamine triethiodide 7.5 mg kg-1 h-1 I.V. and artificially respired. EEG, ECG, end-tidal CO2, lung pressure and deep body temperature were monitored and kept within normal limits. Animals were humanely killed at the end of the experiments. In the G/I laminae we found no difference between AL and AL/L cats but a significant difference between AL/L and KL cats and between AL and KL cats with regard to peak discharge rates and cut-off velocities (Wilcoxon, P < 0.05). Thus it seems that the interval between lesion and experiment is not a critical factor. By contrast, in the SG laminae there was no difference between AL and KL cats with respect to peak discharge rates and cut-off velocities. Thus following monocular retinal lesions there appears to be a critical period for the LPZ cells recorded from the G/I layers of area 17, after which the presumed cortical mechanisms underlying establishment of ectopic RFs are not capable of good compensation for the loss of the retinal input

Laminar differences in plasticity in area 17 following retinal lesions in kittens or adult cats

Circumscribed retinal lesions in adult cats result in a reorganization of circuitry in area 17 such that neurons in the lesion projection zone (LPZ) can now be activated, not from their original receptive fields (RFs) but from regions of normal retina adjacent to the lesion ('ectopic' RFs). We have studied this phenomenon further by making circumscribed monocular retinal lesions in 8-week-old kittens and recording responses to visual stimuli of neurons in the LPZ of area 17 when these cats reached adulthood. These responses have been compared with those in adult-lesioned cats either of relatively short postlesion survival (2–24 weeks) or long postlesion survival (3.5–4.5 years). In both kitten-lesioned and adult-lesioned animals most LPZ neurons recorded from the supragranular layers (II and III) not only exhibited new ectopic RFs when stimuli were presented via the lesioned eye but the RF properties (e.g. the sizes of excitatory RFs, orientation and direction selectivities, velocity preferences and upper cut-off velocities) were often indistinguishable from those seen when stimuli were presented via the nonlesioned eye. Similarly, in both kitten-lesioned and adult-lesioned animals, most LPZ neurons recorded from the granular and infragranular layers (IV, V, VI), like those recorded from the supragranular layers, were binocular. However, in adult-lesioned but not in kitten-lesioned animals, the responses and the upper cut-off velocities of LPZ cells recorded from the granular and infragranular layers to stimuli presented via ectopic RFs tended to be, respectively, substantially weaker and lower than those for stimuli presented via the nonlesioned eye. The age-related laminar differences in reorganizational plasticity of cat striate cortex correlate with the lamino-temporal pattern of distribution of N-methyl-d-aspartate glutamate receptors in striate cortex

Retinal Origin of Electrically Evoked Potentials in Response to Transcorneal Alternating Current Stimulation in the Rat

PURPOSE: Little is known about the physiological mechanisms underlying the reported therapeutic effects of transorbital alternating current stimulation (ACS) in vision restoration, or the origin of the recorded electrically evoked potentials (EEPs) during such stimulation. We examined the issue of EEP origin and electrode configuration for transorbital ACS and characterized the physiological responses to CS in different structures of the visual system. METHODS: We recorded visually evoked potentials (VEPs) and EEPs from the rat retina, visual thalamus, tectum, and visual cortex. The VEPs were evoked by light flashes and EEPs were evoked by electric stimuli delivered by two electrodes placed either together on the same eye or on the eyeball and in the neck. Electrically evoked potentials and VEPs were recorded before and after bilateral intraorbital injections of tetrodotoxin that blocked retinal ganglion cell activity. RESULTS: Tetrodotoxin abolished VEPs at all levels in the visual pathway, confirming successful blockage of ganglion cell activity. Tetrodotoxin also abolished EEPs and this effect was independent of the stimulating electrode configurations. CONCLUSIONS: Transorbital electrically evoked responses in the visual pathway, irrespective of reference electrode placement, are initiated by activation of the retina and not by passive conductance and direct activation of neurons in other visual structures. Thus, placement of stimulating electrodes exclusively around the eyeball may be sufficient to achieve therapeutic effects

Plasticity in adult cat visual cortex (area 17) following circumscribed monocular lesions of all retinal layers

In eight adult cats intense, sharply circumscribed, monocular laser lesions were used to remove all cellular layers of the retina. The extents of the retinal lesions were subsequently confirmed with counts of α-ganglion cells in retinal whole mounts; in some cases these revealed radial segmental degeneration of ganglion cells distal to the lesion.Two to 24 weeks later, area 17 (striate cortex; V1) was studied electrophysiologically in a standard anaesthetized, paralysed (artificially respired) preparation. Recording single- or multineurone activity revealed extensive topographical reorganization within the lesion projection zone (LPZ).Thus, with stimulation of the lesioned eye, about 75 % of single neurones in the LPZ had ‘ectopic’ visual discharge fields which were displaced to normal retina in the immediate vicinity of the lesion.The sizes of the ectopic discharge fields were not significantly different from the sizes of the normal discharge fields. Furthermore, binocular cells recorded from the LPZ, when stimulated via their ectopic receptive fields, exhibited orientation tuning and preferred stimulus velocities which were indistinguishable from those found when the cells were stimulated via the normal eye.However, the responses to stimuli presented via ectopic discharge fields were generally weaker (lower peak discharge rates) than those to presentations via normal discharge fields, and were characterized by a lower-than-normal upper velocity limit.Overall, the properties of the ectopic receptive fields indicate that cortical mechanisms rather than a retinal ‘periphery’ effect underlie the topographic reorganization of area 17 following monocular retinal lesions

Topographic reorganization in area 18 of adult cats following circumscribed monocular retinal lesions in adolescence

Circumscribed laser lesions were made in the nasal retinae of one eye in adolescent cats. Ten to sixteen months later, about 80 % of single neurones recorded in the lesion projection zone (LPZ) of contralateral area 18 (parastriate cortex, area V2) were binocular but when stimulated via the lesioned eye had ectopic discharge fields (displaced to normal retina in the vicinity of the lesion). Although the clear majority of binocular cells recorded from the LPZ responded with higher peak discharge rates to stimuli presented via the non-lesioned eye, the orientation and direction selectivities as well as preferred and upper cut-off velocities for stimuli presented through either eye were very similar. Furthermore, the sizes of the ectopic discharge fields of binocular cells recorded from the LPZ were not significantly different from those of their counterparts plotted via the non-lesioned eye. Thus, monocular retinal lesions performed in adolescent cats induce topographic reorganization in the LPZ of area 18. Although a similar reorganization occurs in area 17 (striate cortex, area V1) of cats in which monocular retinal lesions were made either in adulthood or adolescence, in view of the very different velocity response profiles of ectopic discharge fields in areas 17 and those in area 18, it appears that ectopic discharge fields in area 17 are largely independent of excitatory feedback input from area 18

Spectral characteristics of phase sensitivity and discharge rate of neurons in the ascending tectofugal visual system

Drifting gratings can modulate the activity of visual neurons at the temporal frequency of the stimulus. In order to characterize the temporal frequency modulation in the cat’s ascending tectofugal visual system, we recorded the activity of single neurons in the superior colliculus, the suprageniculate nucleus, and the anterior ectosylvian cortex during visual stimulation with drifting sine-wave gratings. In response to such stimuli, neurons in each structure showed an increase in firing rate and/or oscillatory modulated firing at the temporal frequency of the stimulus (phase sensitivity). To obtain a more complete characterization of the neural responses in spatiotemporal frequency domain, we analyzed the mean firing rate and the strength of the oscillatory modulations measured by the standardized Fourier component of the response at the temporal frequency of the stimulus. We show that the spatiotemporal stimulus parameters that elicit maximal oscillations often differ from those that elicit a maximal discharge rate. Furthermore, the temporal modulation and discharge-rate spectral receptive fields often do not overlap, suggesting that the detection range for visual stimuli provided jointly by modulated and unmodulated response components is larger than the range provided by a one response component.This work was supported by Hungarian Brain Research Program KTIA 13 NAP-A-I/15 grant, OTKA Hungary Grant K83810, Polish National Science Centre Grant N N303 820640, Polish-Hungarian bilateral academic grants for years (2011-2016) and EU FP7 Project, GA No 264173 (Bio-Imagine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript