Adaptation-induced plasticity and spike waveforms in cat visual cortex

Extracellular spikes recorded in the visual cortex (Area 17/18, V1) are commonly classified into either regular-spiking (RS) or fast-spiking (FS). Using multi-electrode arrays positioned in cat V1 and a broadband stimulus, we show that there is also a distinct class with positive-spiking (PS) waveforms. PS units were associated mainly with non-oriented receptive fields while RS and FS units had orientation-selective receptive fields. We suggest that PS units are recordings of axons originating from the thalamus. This conclusion was reinforced by our finding that we could record PS units after cortical silencing, but not record RS and FS units. The importance of our findings is that we were able to correlate spike shapes with receptive field characteristics with high precision using multi-electrode extracellular recording techniques. This allows considerable increases in the amount of information that can be extracted from future cortical experiments. Extracellular spike waveforms from recordings in the visual cortex have been classified into either regular-spiking (RS) or fast-spiking (FS) units. While both these types of spike waveforms are negative-dominant, we show that there are also distinct classes of spike waveforms in visual Area 17/18 (V1) of anaesthetised cats with positive-dominant waveforms, which are not regularly reported. The spatial receptive fields (RFs) of these different spike waveform types were estimated, which objectively revealed the existence of oriented and non-oriented RFs. We found that units with positive-dominant spikes, which have been associated with recordings from axons in the literature, had mostly non-oriented RFs (84%), which are similar to the centre-surround RFs observed in the dorsal lateral geniculate nucleus (dLGN). Thus, we hypothesise that these positive-dominant waveforms may be recordings from dLGN afferents. We recorded from V1 before and after the application of muscimol (a cortical silencer) and found that the positive-dominant spikes (PS) remained while the RS and FS cells did not. We also noted that the PS units had spiking characteristics normally associated with dLGN units (i.e. higher response spike rates, lower response latencies and higher proportion of burst spikes). Our findings show quantitatively that it is possible to correlate the RF properties of cortical neurons with particular spike waveforms. This has implications for how extracellular recordings should be interpreted and complex experiments can now be contemplated that would have been very challenging previously, such as assessing the feedforward connectivity between brain areas in the same location of cortical tissue.

Rearing in darkness slows the time course of the critical period in visual cortex, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, whereas at 20 weeks dark-reared cats are more plastic [G. D. Mower (1991)Dev. Brain Res., 58, 151-158]. Thus, a stringent criterion is that genes that are important for plasticity in visual cortex will show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young vs. older animals. The present study reports the identification by differential display PCR of Dab-1, the mammalian homolog of the drosophila disabled-1 gene, as a candidate gene for critical period neuronal plasticity, expression of which is regulated according to this criterion in cat visual cortex. Evidence for this bidirectional direction regulation is extended to Dab-1 protein in cat and mouse visual cortex and shown to be specific to visual cortex, not occurring in frontal cortex. The Reelin/Dab-1 pathway has well-documented functions in cell migration during prenatal life and increasing evidence indicates that in postnatal brain the pathway plays a role in synaptic plasticity. The present results extend this evidence by directly implicating Dab-1 in postnatal critical period plasticity of visual cortex.

Brief optogenetic stimulation of thalamocortical axons evoked a 400 Hz wavelet, 'ripplet,' in the extracellular field potential in cortical layer 4, together with phase-locked spike bursts in fast-spiking inhibitory interneurons and alternating excitatory and inhibitory synaptic currents in excitatory cells.

Event Abstract Back to Event Orientation adaptation and tilt aftereffect in a network model of primary visual cortex Klaus Wimmer1* and Klaus H. Obermayer1 1 Technische Universität Berlin, Bernstein Center for Computational Neuroscience Berlin and School of Electrical Engineering and Computer Science, Germany The temporal context of a sensory stimulus influences the representation of the stimulus by neural populations and, in turn, the perception of the stimulus. A well studied psychophysical phenomenon is the tilt aftereffect, in which an adapting context stimulus causes a vertically orientated test stimulus to appear repulsed away from the context orientation. Physiological studies have identified the accompanying changes in orientation tuning of individual neurons in primary visual cortex: Tuning curves shift away from the adapting stimulus, and responses close to the adapting stimulus are suppressed-. Previous modeling studies have been purely conceptual or have focused exclusively either on the perceptual (tilt aftereffect) or physiological (tuning curve changes) effects. Here, we investigate whether synaptic plasticity evokes adaptive changes in orientation tuning that correctly predict the magnitude of the tilt aftereffect. We use two-dimensional fire rate models [1] of primary visual cortex that incorporate a biologically plausible topographic orientation preference map. The model cells receive strong recurrent excitation and inhibition, both dominating the feed-forward input, in order to account for fundamental physiological data on orientation tuning. We then systematically vary the strength of synaptic depression for the four types of recurrent connections (exc -> exc, exc -> inh, inh -> inh, and inh -> exc) and simulate adaptation experiments. Depending on the relative strength of the depression parameters, tuning curves of individual cells as well as the population responses show either attractive or repulsive shifts, and adaptation leads either to response suppression or facilitation. A range of models with strong depression of excitatory to excitatory connections is compatible with the experimental data. We additionally investigate how the tuning curve shifts of model neurons depend on the local intercortical interactions. It has been found experimentally, that adaptation-induced changes are more pronounced close to pinwheel centers. In the model, adaptation affects the broadly tuned recurrent inputs near pinwheels more strongly, which in turn leads to larger tuning curve shifts. We do not observe this difference between pinwheel and orientation domain cells in models with weak recurrent interactions. Thus, the pronounced adaptation near pinwheel centers is a consequence of the enhanced sensitivity to modulations of connection strengths in the strong recurrent network regime.

In the intact adult animal, synaptic plasticity in the visual cortex (VC) is a dynamic and naturalistic phenomenon, the mechanisms of which are not yet fully understood. Given its intrinsic role in hippocampal plasticity, we investigated the eVects of pharmacological antagonism of mGluR5 on synaptic plasticity and receptor expression in the VC of freely moving adult pigmented rats, and compared this with hippocampal effects. Persistent long-term potentiation (LTP, >24 h) in layer II/III of the primary VC, and LTP in the dentate gyrus, were impaired by application of the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP). Long-term depression in VC was unaffected. Twenty-four hours after MPEP treatment, mGluR1a monomer expression was reduced in the VC but not in the hippocampus, whereas dimer expression was unaffected; mGluR2/3 and mGluR5 monomers were unaffected, but dimers were reduced in the VC. Our data suggest that mGluR5 is engaged in the regulation of synaptic plasticity in the adult VC and hippocampus: the mechanisms for this may be quite distinct, however. While only LTP is affected by mGluR5-antagonism in the VC, both LTP and LTD are affected in the hippocampus. Furthermore, the higher sensitivity of mGluR expression to antagonism of mGluR5 in VC compared to the hippocampus suggests that mGluR5 regulates plasticity phenomena in these structures by means of distinct mGluR-dependent processes.

Spiking Irregularity and Frequency Modulate the Behavioral Report of Single-Neuron Stimulation

During early postnatal brain development, changes in visual input can lead to specific alteration of function and connectivity in mammalian visual cortex. In cat, this so-called critical period exhibits maximal sensory-driven adaptations around postnatal day 30 (P30), and ceases toward adulthood. We examined the molecular framework that directs age- and experience-dependent plasticity in cat visual cortex, by comparing protein expression profiles at eye opening (postnatal day 10 (P10), when experience-dependent plasticity starts), the peak of the critical period (P30), and in adulthood. Using 2-D DIGE, we performed comparisons of P10-P30 and P30-adult brain protein samples. Sixty protein spots showed statistically significant intensity changes in at least one comparison. Fifty-one spots were identified using quadrupole-TOF MS/MS or LC-MS/MS, containing 37 different proteins. The progressive increase or decrease in protein expression levels could be correlated to age-dependent postnatal brain development. Four spots containing transferrin, 14-3-3 alpha/beta and cypin, showed maximal protein expression levels at P30, thereby showing a positive correlation to critical period plasticity. Western analysis indeed revealed a clear effect of visual deprivation on cypin expression in cat visual cortex. Our results therefore demonstrate the power of 2-D DIGE as a tool toward understanding the molecular basis of nervous system development and plasticity.

While it is known that an epigenetic remodeling of chromatin structure controls developmental plasticity in the visual cortex, three main questions have remained open. Which is the physiological time course of histone modifications? Is it possible, by manipulating the chromatin epigenetic state, to modulate plasticity levels during the critical period? How can we regulate histone acetylation in the adult brain in a noninvasive manner? We show that the early exposure of rat pups to enriching environmental conditions accelerates the critical period for plasticity in the primary visual cortex, linking this effect to increased histone acetylation, specifically at the BDNF gene level. Moreover, we report that the exposure of adult animals to environmental enrichment enhances histone acetylation and reopens juvenile-like plasticity.

Sharp electrodes were used to record light-evoked postsynaptic potentials (PSPs) from neurons in turtle visual cortex in an in vitro preparation of the geniculocortical pathway. Neurons were placed into four groups based on the firing patterns produced by intracellular current injections: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH) cells. RS cells have been shown to be pyramidal cells while FS cells are typically interneurons. Light stimuli were diffuse, 1-s flashes of 640-nm light with intensities (I) varying from 0 to 10(4) photons microm(-2) s(-1). The response (R) in each case was the maximal amplitude of the light-evoked depolarizing PSP. Cells of all four types showed sigmoidal intensity-response (IR) functions with a linear rising phase for stimuli above the intensity threshold followed by saturation at high light intensities. Responses at high intensities were variable and some cells showed indications of supersaturation. Light-evoked PSPs had longer latencies and times-to-peak response in RS cells than they did in FS cells. RS cells fired action potentials as much as 200 ms later than did FS cells. Since responses recorded in RS cells at light intensities just above threshold are unlikely to involve contributions from other pyramidal cells, these data indicate that the geniculocortical or feedforward pathway to pyramidal cells has a high gain. The fact that FS cells fire well before RS cells suggests that feedforward inhibition plays a role in controlling the gain of the geniculocortical pathway.

Orientation selectivity of neurons in the primary visual cortex is thought to be an important requisite for the preprocessing of visual information, which is followed by more complex information processing and representation in the extrastriate cortex for visual perception. It is widely accepted that neurons in the primary visual cortex optimally responding to similar stimulus orientations are clustered in a manner of straight columns extending from the superficial to deep layers (Hubel & Wiesel, 1962, 1963a). The cerebral cortex is, however, folded inside a skull, which makes gyri and fundi. Particularly, in cats, area 17 (primary visual cortex) is located on the curved cortex called the lateral gyrus (Tusa et al., 1978). These facts raise questions of how the tangential arrangement of orientation columns is reconciled with the curvature of the gyrus, and whether the columns penetrate the cortex from the superficial to deep layers. In the first part of this chapter, we show a possible configuration of feature representation in the visual cortex using a three-dimensional (3D) self-organization model, and then confirm the predicted 3D orientation representation using multi-slice, high-resolution functional magnetic resonance imaging (fMRI) performed in the cat visual cortex (Tanaka et al., 2011). We obtained a close agreement in orientation representation between theoretical predictions and experimental observations. These studies demonstrated that in the curved cortex, preferred orientations are represented by wedgelike orientation columns which do not necessarily penetrate from superficial to deep layers, whereas in the flat cortex, preferred orientations are tended to be represented by classical straight columns.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that uses low-amplitude currents to generate low electric fields in the brain, influencing cognition, motor skills, and behavior. Despite its potential, the neural mechanisms underlying tDCS remain unclear, in part because many prior studies have used electric field strengths (10-40V/m) in animal models that exceed those typically achieved in humans. To better characterize how cortical neurons respond across a range of electric field strengths, we developed an in-vivo rat model to examine the effects of both low and high electric fields. Currents of 0.005-0.3mA were applied in 9 rats, generating electric fields of 0.5-35V/m in the somatosensory cortex. In an anesthetized rat model, we recorded neural activity across cortical layers with a multichannel silicone probe. Somatosensory evoked potentials (SSEP) elicited by foot shocks were recorded, and spike waveforms were used to distinguish regular spiking (RS) and fast-spiking (FS) neurons. Anodal tDCS was associated with SSEP hyperpolarization in superficial cortical regions and depolarization in deeper regions, with cathodal stimulation producing an asymmetric reversal of this pattern. Changes in spiking activity were observed in RS neurons at lower electric fields, whereas higher field strengths were required to influence spiking activity in FS neurons. Across measures, effect magnitudes scaled with electric field strength and were well described by linear mixed-effects models. Changes in spiking activity were correlated with changes in SSEP polarity. These findings demonstrate that electric field-dependent modulation of cortical activity can be detected in vivo across a wide range of stimulation intensities, including weak fields comparable to those induced by human tDCS, although effects are substantially larger at higher field strengths. This work provides direct in-vivo evidence linking cortical polarization to changes in neuronal spiking and helps constrain mechanistic interpretations of tDCS effects observed in humans.

The correlation between cortical neuron maturation and neurofilament phosphorylation: a developmental study of phosphorylated 200 kDa neurofilament protein in cat visual cortex

BackgroundSensory neurons display transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In adult cat primary visual cortex, orientation-selective neurons shift their preferred orientation after being adapted to a non-preferred orientation. The direction of those shifts, towards (attractive) or away (repulsive) from the adapter depends mostly on adaptation duration. How the adaptive behavior of a neuron is related to that of its neighbors remains unclear.ResultsHere we show that in most cases (75%), cells shift their preferred orientation in the same direction as their neighbors. We also found that cells shifting preferred orientation differently from their neighbors (25%) display three interesting properties: (i) larger variance of absolute shift amplitude, (ii) wider tuning bandwidth and (iii) larger range of preferred orientations among the cluster of cells. Several response properties of V1 neurons depend on their location within the cortical orientation map. Our results suggest that recording sites with both attractive and repulsive shifts following adaptation may be located in close proximity to iso-orientation domain boundaries or pinwheel centers. Indeed, those regions have a more diverse orientation distribution of local inputs that could account for the three properties above. On the other hand, sites with all cells shifting their preferred orientation in the same direction could be located within iso-orientation domains.ConclusionsOur results suggest that the direction and amplitude of orientation preference shifts in V1 depend on location within the orientation map. This anisotropy of adaptation-induced plasticity, comparable to that of the visual cortex itself, could have important implications for our understanding of visual adaptation at the psychophysical level.

Requirement of keratan sulfate proteoglycan phosphacan with a specific sulfation pattern for critical period plasticity in the visual cortex

During the analysis of neurobiological signals acquired during neurosurgical procedures such as Deep Brain Stimulation, one focuses mainly on the signal’s background and spiking activity. Spikes, the electrical impulses generated by neuron cells, are events lasting about 1.5 ms with voltage typically well below 200 \(\upmu \)V. As the shape of spike derives from the physical construction of the neuron’s cell membrane and its distance from the recording point, one can infer that spikes of different shapes were generated by different neuron cells. This information can be beneficial during the analysis of the acquired signals, and the procedure of grouping spikes according to their shapes, is called spike sorting. Typically in this procedure, there are defined various attributes characterizing spike shape, and subsequently, the standard clustering method is used to produce groups of spikes of different shapes. This may cause some difficulties that arise both from the definition of good discriminating attributes as well as from the fact that one does not know beforehand how many clusters of shapes to expect. The approach presented in this paper is different, using the fully unsupervised and explainable AI, it generates groups of spike shapes in a fully automatic way. No attributes have to be defined nor the expected number of shape clusters provided. Spike waveforms are fed into the autoencoder that has defined additional constraints on its latent layers. After training, data obtained from those layers can be used for the purpose of spike shape clustering. Beside shape class, one also receives information on how much given spike shape differs from the mean shape of its class.