Tectal Responses Research Articles

BRCA1 and ELK-1 regulate neural progenitor cell fate in the optic tectum in response to visual experience in Xenopus laevis tadpoles.

In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

Recurrent network interactions explain tectal response variability and experience-dependent behavior.

Response variability is an essential and universal feature of sensory processing and behavior. It arises from fluctuations in the internal state of the brain, which modulate how sensory information is represented and transformed to guide behavioral actions. In part, brain state is shaped by recent network activity, fed back through recurrent connections to modulate neuronal excitability. However, the degree to which these interactions influence response variability and the spatial and temporal scales across which they operate, are poorly understood. Here, we combined population recordings and modeling to gain insights into how neuronal activity modulates network state and thereby impacts visually evoked activity and behavior. First, we performed cellular-resolution calcium imaging of the optic tectum to monitor ongoing activity, the pattern of which is both a cause and consequence of changes in network state. We developed a minimal network model incorporating fast, short range, recurrent excitation and long-lasting, activity-dependent suppression that reproduced a hallmark property of tectal activity - intermittent bursting. We next used the model to estimate the excitability state of tectal neurons based on recent activity history and found that this explained a portion of the trial-to-trial variability in visually evoked responses, as well as spatially selective response adaptation. Moreover, these dynamics also predicted behavioral trends such as selective habituation of visually evoked prey-catching. Overall, we demonstrate that a simple recurrent interaction motif can be used to estimate the effect of activity upon the incidental state of a neural network and account for experience-dependent effects on sensory encoding and visually guided behavior.

A Moving Target Detection Model Inspired by Spatio-Temporal Information Accumulation of Avian Tectal Neurons

Moving target detection in cluttered backgrounds is always considered a challenging problem for artificial visual systems, but it is an innate instinct of many animal species, especially the avian. It has been reported that spatio-temporal information accumulation computation may contribute to the high efficiency and sensitivity of avian tectal neurons in detecting moving targets. However, its functional roles for moving target detection are not clear. Here we established a novel computational model for detecting moving targets. The proposed model mainly consists of three layers: retina layer, superficial layers of optic tectum, and intermediate-deep layers of optic tectum; in the last of which motion information would be enhanced by the accumulation process. The validity and reliability of this model were tested on synthetic videos and natural scenes. Compared to EMD, without the process of information accumulation, this model satisfactorily reproduces the characteristics of tectal response. Furthermore, experimental results showed the proposed model has significant improvements over existing models (EMD, DSTMD, and STMD plus) on STNS and RIST datasets. These findings do not only contribute to the understanding of the complicated processing of visual motion in avians, but also further provide a potential solution for detecting moving targets against cluttered environments.

Comparison of pop-out responses to luminance and motion contrasting stimuli of tectal neurons in pigeons

The emergence of visual saliency has been widely studied in the primary visual cortex and the superior colliculus (SC) in mammals. There are fewer studies on the pop-out response to motion direction contrasting stimuli taken in the optic tectum (OT, homologous to mammalian SC), and these are mainly of owls and fish. To our knowledge the influence of spatial luminance has not been reported. In this study, we have recorded multi-units in pigeon OT and analyzed the tectal response to spatial luminance contrasting, motion direction contrasting, and contrasting stimuli from both feature dimensions. The comparison results showed that 1) the tectal response would pop-out in either motion direction or spatial luminance contrasting conditions. 2) The modulation from motion direction contrasting was independent of the temporal luminance variation of the visual stimuli. 3) When both spatial luminance and motion direction were salient, the response of tectal neurons was modulated more intensely by motion direction than by spatial luminance. The phenomenon was consistent with the innate instinct of avians in their natural environment. This study will help to deepen the understanding of mechanisms involved in bottom-up visual information processing and selective attention in the avian.

NMDARs Translate Sequential Temporal Information into Spatial Maps.

SummarySpatial representations of the sensory world are important for brain function. Timing is an essential component of sensory information. Many brain circuits transform the temporal sequence of input activity into spatial maps; however, the mechanisms underlying this transformation are unclear. Different N-methyl-D-aspartate receptor (NMDAR) response magnitudes result in synaptic potentiation or depression. We asked whether NMDAR response magnitude also affects the transformation of temporal information into directional spatial maps. We quantified retinotectal axon branch dynamics in Xenopus optic tectum in response to temporal sequences of visual stimulation. Reducing NMDAR responses by 50% inverts the spatial distribution of branch dynamics along the rostrocaudal axis in response to temporal patterns of input, suggesting that the magnitude of NMDAR signaling encodes the temporal sequence of inputs and translates the temporal code into a directional spatial map using structural plasticity-based branch dynamics. We discuss how this NMDAR-dependent decoding mechanism retrieves spatial information from sequential afferent activity.

Luminance Changes Drive Directional Startle through a Thalamic Pathway

Looming visual stimuli result in escape responses that are conserved from insects to humans. Despite their importance for survival, the circuits mediating visual startle have only recently been explored in vertebrates. Here we show that the zebrafish thalamus is a luminance detector critical to visual escape. Thalamic projection neurons deliver dim-specific information to the optic tectum, and ablations of these projections disrupt normal tectal responses to looms. Without this information, larvae are less likely to escape from dark looming stimuli and lose the ability to escape away from the source of the loom. Remarkably, when paired with an isoluminant loom stimulus to the opposite eye, dimming is sufficient to increase startle probability and to reverse the direction of the escape so that it is toward the loom. We suggest that bilateral comparisons of luminance, relayed from the thalamus to the tectum, facilitate escape responses and are essential for their directionality.

Limitations of Neural Map Topography for Decoding Spatial Information.

Topographic maps are common throughout the nervous system, yet their functional role is still unclear. In particular, whether they are necessary for decoding sensory stimuli is unknown. Here we examined this question by recording population activity at the cellular level from the larval zebrafish tectum in response to visual stimuli at three closely spaced locations in the visual field. Due to map imprecision, nearby stimulus locations produced intermingled tectal responses, and decoding based on map topography yielded an accuracy of only 64%. In contrast, maximum likelihood decoding of stimulus location based on the statistics of the evoked activity, while ignoring any information about the locations of neurons in the map, yielded an accuracy close to 100%. A simple computational model of the zebrafish visual system reproduced these results. Although topography is a useful initial decoding strategy, we suggest it may be replaced by better methods following visual experience. A very common feature of brain wiring is that neighboring points on a sensory surface (eg, the retina) are connected to neighboring points in the brain. It is often assumed that this "topography" of wiring is essential for decoding sensory stimuli. However, here we show in the developing zebrafish that topographic decoding performs very poorly compared with methods that do not rely on topography. This suggests that, although wiring topography could provide a starting point for decoding at a very early stage in development, it may be replaced by more accurate methods as the animal gains experience of the world.

Functional Profiles of Visual-, Auditory-, and Water Flow-Responsive Neurons in the Zebrafish Tectum

The tectum has long been known as a hub of visual processing, and recent studies have elucidated many of the circuit-level mechanisms by which tectal neurons filter visual information. Here, we use population-scale imaging of tectal neurons expressing a genetically encoded calcium indicator to characterize tectal responses to non-visual stimuli in zebrafish. We identify ensembles of neurons responsive to stimuli for each of three sensory modalities: vision, audition, and water flow sensation. These ensembles display consistently represented response profiles to our stimuli, and each has a preferred stimulus and salient feature to which it is most responsive. Each sensory modality drives a unique spatial profile of activity in the tectal neuropil, suggesting that the neuropil's laminar structure functionally subserves multiple modalities. The positions of the responsive neurons in the periventricular layer are also distinct across modalities, and very few neurons are responsive to multiple modalities. The cells contributing to each ensemble are highly variable from trial to trial, but ensembles contain "cores" of reliably responsive cells, suggesting a mechanism whereby they could maintain consistency in reporting salient stimulus features while retaining flexibility to report on similar stimuli. Finally, we find that co-presentation of auditory or water flow stimuli suppress visual responses in the tectum.

Nicotinic potentiation of frog retinotectal transmission in tectum layer F by α3β2, α4β2, α2β4, α6β2, or α7 acetylcholine receptor subtypes

ObjectiveThe aim of the study was to explore the effect of semi-specific antagonists and agonists of the nicotinic acetylcholine receptors on the paired-pulse facilitation and nicotinic tonic and phasic potentiation of the frog retinotectal synaptic transmission. Materials and methodsThe experiments were performed in vivo on adult frogs, Rana temporaria. An individual retina ganglion cell (or its retinotectal fiber) was stimulated by current pulses delivered through multichannel stimulating electrode positioned on the retina. Responses to a discharge of a single retinal ganglion cell were recorded in the tectum by an extracellular carbon-fiber microelectrode positioned in the terminal arborization of the retinotectal fiber in the tectum layer F. The effect of the antagonists and agonists of the nicotinic acetylcholine receptors on the tectal responses has been tested. ResultsWe found that the antagonists, MLA and DHβE, and agonists, RJR-2403 and choline, of the nicotinic acetylcholine receptors of the α3β2, α4β2, α2β4, α6β2 or α7 subtypes have had no effect on the phasic and tonic potentiation of the retinotectal transmission. The paired-pulse facilitation of the retinotectal transmission was not appreciably affected by the antagonists, but the choline, agonist of the α7 subtype receptor, has significantly decreased the paired-pulse facilitation. ConclusionsThe tonic and phasic potentiation of the retinotectal transmission in the tectum layer F were not mediated by the receptors of α3β2, α4β2, α2β4, α6β2 or α7 subtype. The results suggest that presynaptic nicotinic acetylcholine receptors of the frog optic fibers are different from those of the mammalian optic fibers.

Local cholinergic interneurons modulate GABAergic inhibition in the chicken optic tectum

The chicken optic tectum (TeO) and its mammalian counterpart, the superior colliculus, are important sensory integration centers. Multimodal information is represented in a topographic map, which plays a role in spatial attention and orientation movements. The TeO is organised in 15 layers with clear input and output regions, and further interconnected with the isthmic nuclei (NI), which modulate the response in a winner-takes-all fashion. While many studies have analysed tectal cell types and their modulation from the isthmic system physiologically, little is known about local network activity and its modulation in the tectum. We have recently shown with voltage-sensitive dye imaging that electrical stimulation of the retinorecipient layers results in a stereotypic response, which is under inhibitory control [S. Weigel & H. Luksch (2012) J. Neurophysiol., 107, 640-648]. Here, we analysed the contribution of acetylcholine (ACh) and the NI to evoked tectal responses using a pharmacological approach in a midbrain slice preparation. Application of the nicotinic ACh receptor (AChR) antagonist curarine increased the tectal response in amplitude, duration and lateral extent. This effect was similar but less pronounced when γ-aminobutyric acid(A) receptors were blocked, indicating interaction of inhibitory and cholinergic neurons. The muscarinic AChR antagonist atropine did not change the response pattern. Removal of the NI, which are thought to be the major source of cholinergic input to the TeO, reduced the response only slightly and did not result in a disinhibition. Based on the data presented here and the neuroanatomical literature of the avian TeO, we propose a model of the underlying local circuitry.

Real-Time Visualization of Neuronal Activity during Perception

To understand how the brain perceives the external world, it is desirable to observe neuronal activity in the brain in real time during perception. The zebrafish is a suitable model animal for fluorescence imaging studies to visualize neuronal activity because its body is transparent through the embryonic and larval stages. Imaging studies have been carried out to monitor neuronal activity in the larval spinal cord and brain using Ca(2+) indicator dyes and DNA-encoded Ca(2+) indicators, such as Cameleon, GFP-aequorin, and GCaMPs. However, temporal and spatial resolution and sensitivity of these tools are still limited, and imaging of brain activity during perception of a natural object has not yet been demonstrated. Here we demonstrate visualization of neuronal activity in the optic tectum of larval zebrafish by genetically expressing the new version of GCaMP. First, we demonstrate Ca(2+) transients in the tectum evoked by a moving spot on a display and identify direction-selective neurons. Second, we show tectal activity during perception of a natural object, a swimming paramecium, revealing a functional visuotopic map. Finally, we image the tectal responses of a free-swimming larval fish to a paramecium and thereby correlate neuronal activity in the brain with prey capture behavior.

Stimulus-Specific Adaptations in the Gaze Control System of the Barn Owl

Abrupt orientation to novel stimuli is a critical, memory-dependent task performed by the brain. In the present study, we examined two gaze control centers of the barn owl: the optic tectum (OT) and the arcopallium gaze fields (AGFs). Responses of neurons to long sequences of dichotic sound bursts comprised of two sounds differing in the probability of appearance were analyzed. We report that auditory neurons in the OT and in the AGFs tend to respond stronger to rarely presented sounds (novel sounds) than to the same sounds when presented frequently. This history-dependent phenomenon, known as stimulus-specific adaptation (SSA), was demonstrated for rare sound frequencies, binaural localization cues [interaural time difference (ITD) and level difference (ILD)] and sound amplitudes. The manifestation of SSA in such a variety of independent acoustic features, in the midbrain and in the forebrain, supports the notion that SSA is involved in sensory memory and novelty detection. To track the origin of SSA, we analyzed responses of neurons in the external nucleus of the inferior colliculus (ICX; the source of auditory input to the OT) to similar sequences of sound bursts. Neurons in the ICX responded stronger to rare sound frequencies, but did not respond differently to rare ITDs, ILDs, or sound amplitudes. We hypothesize that part of the SSA reported here is computed in high-level networks, giving rise to novelty signals that modulate tectal responses in a context-dependent manner.

Pretectal influences on tectal response of the frog: Intracellular recording and field potentials analysis

Synaptic organization and spatiotemporal pattern of the tectal response to electrical stimulation of pretectal (Lpd/P) nuclei were examined in the bullfrog (Rana catesbeiana) by means of intracellular study and a current source density (CSD) analysis. The pretectal stimulation elicited mainly two types of responses (EI; I type) in the ipsilateral tectum, only one type of response (I type) in the contralateral tectum. EPSPs with short latencies were concluded to be monosynaptic. Most IPSPs were generated through di- or polysynaptic paths, but monosynaptic IPSPs were also recorded in both optic tecta. The antidromically invaded tecto-pretectal projecting cells were recorded in both tecta, which revealed reciprocal connections between the tectum and particular pretectal nuclei. In all CSD profiles, only one type of spatiotemporal pattern composed of one sink with short latency was observed. The short-latency sinks appear to be associated with monosynaptic activity generated by the pretectal inputs. The CSD analysis results show good accordance with the intracellular study.

Tectal responses to potassium loads and subsequent visual stimuli in the toad, Bufo bufo

Calling male toads were tested behaviourally for their prey catching responses to wormlike stimuli and assigned to groups of non-hungry and hungry depending on their prey catching motivation before being prepared for visual unit, massed unit and slow potential shift (SPS) recording from the optic tectum. Control recordings to visual stimuli were made before recording the effects of application of isotonic solutions containing concentrations of 0–41 mM K +. Application of solution was followed by presentation of the visual stimulus while the solution still bathed the tectum. The best tectal responses were made to large square visual stimuli in the non-hungry toads, perhaps because recordings were made in the breeding season. Responses of the tectum to solution addition were significant in the concentration range of 7–17 mM K +. Hungry toads showed an earlier, smaller response than non-hungry (sexually motivated) animals. When the visual stimulus was presented, there were unit and massed unit responses at all bathing solution concentrations, which were larger in non-hungry animals. These experiments revealed that toads motivated to feed respond earlier than non-hungry toads to application of artificial CSF to the tectum, though non-hungry toads responded best to the subsequent visual stimulus.

Visual processing of the zebrafish optic tectum before and after optic nerve damage.

Although the zebrafish has become an important model in visual neuroscience, little has been done to examine the processing of its higher visual centers. The purpose of this work was twofold. The first purpose was to examine the physiology of the zebrafish retinotectal system and its relationship to retinal physiology. Spectral sensitivity functions were derived from visually evoked tectal responses and these functions were compared to the functions of electroretinogram (ERG) responses obtained using the same stimulus conditions. The second purpose was to examine the recovery of visual functioning of the tectum following optic nerve damage. The optic nerves of adult zebrafish were damaged (crushed), and tectal visual processing was assessed following damage. The results showed that the spectral sensitivity functions based on the On-responses of the tectum and ERG were qualitatively similar. The functions based on each response type received similar cone contributions including both nonopponent and opponent contributions. However, the spectral sensitivity functions based on the Off-responses of the tectum and ERG differed. The results also showed that the zebrafish visual system is capable of neural regeneration. By 90 days following an optic nerve crush, the spectral sensitivity function based on the tectal On-response was similar to functions obtained from normal zebrafish. Although the tectal Off-response did recover, the spectral sensitivity based on the Off-response was not the same as the function of normal zebrafish. These results support the notion that different levels of the visual system process information differently and that the zebrafish visual system, like those of other lower vertebrates, is capable of functional regeneration.

Sensory response patterns and the evolution of visual signal design in anoline lizards

The evolutionary relationship between visual system response and visual signal design was investigated in four species of anoline lizards which occupy distinctly different habitats. Anoles display with motion patterns of a colorful throat fan called the dewlap. We assessed signal visibility by recording evoked potentials from the optic tectum in response to a moving stimulus flag (a dewlap-like stimulus), and, in one species, by testing behavioral response. The motion pattern, intensity and spectral quality of the stimulus flag, and the background against which it was viewed, were independently manipulated. In all cases, high-velocity motion patterns with a high percentage of brightness contrast between stimulus and background produced the greatest response. Differences in spectral quality between stimulus and background (color contrast) had no effect on tectal responses, but did influence the behaviorally measured detection probability. Using habitat light data we estimated the visibility of the dewlap of each species in different natural habitats. Each species' dewlap was highly visible in its own habitat, but some were much less visible in the habitats of some other species. Habitat light conditions and visual system response properties appear to have constrained the evolution of dewlap design, in at least some of the species.

Ultrastructure and GABA immunoreactivity in layers 8 and 9 of the optic tectum of Xenopus laevis.

This study presents an ultrastructural analysis of layers 8 and 9 in the optic tectum of Xenopus laevis. Retinotectal axons were labelled with horseradish peroxidase and tectal cells were labelled with antibody to GABA. Four distinct axonal and dendritic structures were identified. GABA-negative axon terminals formed asymmetric synapses and were categorized as type a-1 (which included retinotectal axons), characterized by medium size synaptic vesicles and pale mitochondria, and type a-2 (non-retinotectal) with large vesicles and dense mitochondria. GABA-negative dendrites (type d) contained dense mitochondria, microtubules in the dendritic shafts, and dendritic spines devoid of microtubules. GABA-positive structures contained small synaptic vesicles and dense mitochondria. Some dendrites (type D) were not only postsynaptic but were also presynaptic elements, as defined by the presence of vesicles and distinct synaptic clefts with symmetric specializations. GABA-positive presynaptic structures were mostly located in vesicle-filled, bulbous extensions of dendritic shafts and usually terminated onto dendritic spines. Some type D dendrites were the middle element in serial synapses, with input from either GABA-positive or GABA-negative structures and output to GABA-negative structures. Retinotectal terminals were identified as one of the synaptic inputs to GABA-positive processes. Glia were characterized by granular cytoplasm and large mitochondria, often displaying a crystalline matrix structure. These results indicate that GABA-positive neurons are a prominent component of circuitry in the superficial layers of the tectum of Xenopus and that, as in mammals, they participate in serial synaptic arrangements in which retinotectal axons are the first element. These arrangements are consistent with complex processing of visual input to the tectum and a central role for inhibitory processes in the shaping of tectal responses.

Early monaural occlusion alters the neural map of interaural level differences in the inferior colliculus of the barn owl

Monaural occlusion during early life causes adaptive changes in the tuning of units in the owl's optic tectum to interaural level differences (ILD) that tend to align teh auditory with the visual map of space. We investigated whether these changes could be due to experience-dependent plasticity occuring in the auditory pathway prior to the optic tectum. Units were recorded in the external nucleus of the inferior colliculus (ICx), which is a major source of auditory input to the optic tectum. The tuning of ICx units to ILD was measured in normal barn owls and in barn owls raised with one ear occluded. ILD tuning at each recording site was measured with dichotic noise bursts, presented at a constant average binaural level, 20 dB above threshold. The best ILD at each site was defined as the midpoint of the range of ILD values which elicited more than 50% of the maximum response. A physiological map of ILD was found in the ICx of normal owls: best ILDs changed systematically from right-ear-greater to left-ear-greater as the electrode progressed from dorsal to ventral. Best ILDs ranged from 13 dB right-ear-greater to 15 dB left-ear-greater and progressed at an average rate of 12 dB/mm. The representations of ILD were similar on both sides of the brain. In the ICx of owls raised with one ear occluded, the map of ILD was shifted in the adaptive direction: ILD tuning was shifted towards values favoring the non-occluded ear (the direction that would restore a normal space map). The average magnitude of the shift was on the order of 8–10 dB in each of 4 owls. In one owl, the mean shift in ILD tuning was almost identical on both sides of the brain. In another owl, the mean shift was much larger on the side ipsilateral to the occlusion than on the contralateral side. In both cases, the mean shifts measured in each ICx were comparable to the mean shifts measured in the optic tectum on the same sides of the brain. Thus, the adjustments in ILD tuning that have been observed in the optic tectum in response to monaural occlusion are almost entirely due to adaptive mechanisms that operate at or before the level of the ICx.

Visually Triggered Neuronal Oscillations in the Pigeon: An Autocorrelation Study of Tectal Activity

In this study we describe visually triggered gamma oscillations in the optic tectum of awake pigeons. This study was motivated by the potential relevance of synchronous oscillatory responses in perceptual binding in a laminated structure other than the mammalian neocortex. Tectal responses were recorded as local field potential and multiunit activity by differential filtering. The local field potential was analysed by computing its autocorrelation function and spectral power with a moving window applied to single response sweeps. The temporal structure of the spike trains was evaluated by computing averaged autocorrelograms. A damped sine wave function was fitted to the autocorrelograms in order to quantify the degree of oscillation of both signals. Epochs of significant oscillatory activity were observed in the local field potential in 60% of the trials (n = 39). In all trials, significant oscillations occupied approximately 10% of the time the stimulus was present. The oscillatory events in both the local field potential and the multiunit activity had frequencies in the range of 20-50 Hz. It is important to emphasize the great variability in the frequency and in the probability of occurrence of the oscillatory responses from trial to trial, which makes the oscillatory behaviour of the tectal activity highly non-stationary. The oscillatory activity we describe in the avian tectum has characteristics similar to those reported in the mammalian neocortex. These findings from a fully awake animal strengthen the universality of oscillations as a possible carrier for synchronization of activity in the constitution of neuronal assemblies.

Plurality of Viual Mismatch Potentials in a Reptile

Abstract Studies with auditory stimuli have established in humans that a mismatch potential (MMP) is elicited whenever a deviant stimulus is substituted for a standard stimulus in a train of monotonous standard stimuli presented at rates > 0.25 Hz. The MMP in humans is localized in the auditory cortex and is known as mismatch negativily, from its polarity in scalp recordings. It is hypothesized to reflect the operation of sensory memory and to be a necessary component of the auditory orienting response. To examine the generality of MMPs we used a visual mismatch paradigm with pond turtles (Pseudemys scripta) while recording with electrode arrays (200 μm spacing) from near surface and deep visual projection areas within the forebrain and optic tectum. Standard stimuli were 10-sec trains of diffused strobe flashes presented at rates of 1-6 Hz against backgrounds of 2-11 lux. Deviant stimuli were brighter or dimmer flashes that followed the last standard flash. MMps were separated from visual evoked potentials by subtracting the response to the last standard flash of the train from the response to the same flash (bright or dim) when delivered as a deviant. Comparisons were also made with evoked potentials to isolated bright or dim flashes, that is, equal in frequency (1 per 12 sec) to the deviants but without intervening standard flashes. At tectal loci bright and dim deviants elicited net positivities that reached statistical significance in the period between 141 ± 8 and 184 ± 12 msec after the deviant stimulus (mean ± SEM). Earlier components in the tectal responses correlated with the intensity of the stimulus rather than its deviance. In the case of the bright deviants the early waves (P50-P75) were larger in amplitude. Forebrain recordings showed a similar although broader period of net positivity, associated with deviance, between 129 ± 8 and 195 ± 12 msec. Deviants, delivered as isolated flash responses evoked larger early components (100-140 msec). In separate experiments with cortical epipial electrodes, a condition somewhat more comparable to scalp recording, MMPs were similar in latency but had a negative polarity. Regression analyses revealed a relationship between the amplitude (base-to-peak) of the MMF' and the degree to which the standard response had declined with repeated stimulation. Rate decrement, as measured by the isolated (long ISI) flash response minus the last standard response, was a significant predictor of MMP amplitudes (r(2) = 0.37, tectum; r(2) = 0.31, forebrain), whereas standard response amplitudes alone were not (r(2) = 0.09; r(2) = 0.06). MMPs are present in nonmammals plurally, that is, at different levels of the visual system, at least as early as the tectum. The existence of subcortical MMPs caution against assigning a primary or exclusive role to those recorded from the cortex.