Optical imaging of the intrinsic signal as a tool to characterize orientation sensitivity in the primary visual cortex of the young mouse.

We employed intrinsic signal optical imaging (ISOI) to investigate orientation sensitivity bias in the visual cortex of young mice. Optical signals were recorded in response to the moving light gratings stimulating ipsi­, contra­ and binocular eye inputs. ISOI allowed visualization of cortical areas activated by gratings of specific orientation and temporal changes of light scatter during visual stimulation. These results confirmed ISOI as a reliable technique for imaging the activity of large populations of neurons in the mouse visual cortex. Our results revealed that the contralateral ocular input activated a larger area of the primary visual cortex than the ipsilateral input, and caused the highest response amplitudes of light scatter signals to all ocular inputs. Horizontal gratings moved in vertical orientation induced the most significant changes in light scatter when presented contralaterally and binocularly, surpassing stimulations by vertical or oblique gratings. These observations suggest dedicated integration mechanisms for the combined inputs from both eyes. We also explored the relationship between point luminance change (PLC) of grating stimuli and ISOI time courses under various orientations of movements of the gratings and ocular inputs, finding higher cross-correlation values for cardinal orientations and ipsilateral inputs. These findings suggested specific activation of different neuronal assemblies within the mouse's primary visual cortex by grating stimuli of the corresponding orientation. However, further investigations are needed to examine this summation hypothesis. Our study highlights the potential of optical imaging as a valuable tool for exploring functional­anatomical relationships in the mouse visual system.

Conditioning­induced changes in sensory cortical maps detected in mice by intrinsic signal optical imaging.

Intrinsic signal optical imaging (ISOI) has been used previously for the detection of changes in sensory processing in the somatosensory cortex in response to environment alteration or after deprivation of sensory information. To date, there have been no reports of ISOI being used in learning­induced changes in the somatosensory cortex. In the present study, ISOI was performed twice in the same mouse: before and after conditional fear learning. The conditioning paradigm consisted of pairing sensory stimulation of vibrissae with electric tail shock. In order to map the cortical representation of the vibrissa B1 with ISOI, we deflected the vibrissa with an intensive stimulation (frequency of 10 Hz for 6 s). After conditioning, we found that the cortical representation of vibrissa B1 had expanded by an average of 44%, compared with pre­learning, by using images obtained with ISOI. Previously, we demonstrated an enlargement of the cortical representation of the vibrissae stimulated by the same behavioral training paradigm but using [14C]2­deoxyglucose. This current investigation provides the first ISOI­based evidence of learning­induced changes in plasticity in the barrel cortex. The results indicate that irrespective of physiological mechanisms used for visualization of the vibrissae representation or subject's testing state (aware or anesthetized animal), the conditioning induced changes in each case in the cortical processing of intensive stimuli. This suggests specific functional reorganization of the neuronal circuits. Moreover, ISOI as a noninvasive method of mapping cortical activation in the same animal before and after behavioral training could serve as a very useful tool for precise manipulation within the cortex and for assessing the resulting effects on experience­dependent cortical plasticity.

Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases.

Neural plasticity-the ability to alter a neuronal response to environmental stimuli-is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer's disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including ß-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians' diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma.

Intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury (ONI) or laser-induced ocular hypertension (OHT). In models of glaucoma, BDNF therapy can delay or halt RGCs loss, but this protection is time-limited. The decreased efficacy of BDNF supplementation has been in part attributed to BDNF TrkB receptor downregulation. However, whether BDNF overexpression causes TrkB downregulation, impairing long-term BDNF signaling in the retina, has not been conclusively proven. After ONI or OHT, when increased retinal BDNF was detected, a concomitant increase, no change or a decrease in TrkB was reported. We examined quantitatively the retinal concentrations of the TrkB protein in relation to BDNF, in a course of adeno-associated viral vector gene therapy (AAV2-BDNF), using a microbead trabecular occlusion model of glaucoma. We show that unilateral glaucoma, with intraocular pressure ( IOP) increased for five weeks, leads to a bilateral decrease of BDNF in the retina at six weeks, accompanied by up to four-fold TrkB upregulation, while a moderate BDNF overexpression in a glaucomatous eye triggers changes that restore normal TrkB concentrations, driving signaling towards long-term RGCs neuroprotection. We conclude that for glaucoma therapy, the careful selection of the appropriate BDNF concentration is the main factor securing the long-term responsiveness of RGCs and the maintenance of normal TrkB levels.

Removal of the Sinusoidal Transorbital Alternating Current Stimulation Artifact From Simultaneous EEG Recordings: Effects of Simple Moving Average Parameters.

Alternating current stimulation is a promising method for the study and treatment of various visual neurological dysfunctions as well as progressive understanding of the healthy brain. Unfortunately, due to the current stimulation artifact, problems remain in the context of analysis of the electroencephalography (EEG) signal recorded during ongoing stimulation. To address this problem, we propose the use of a simple moving average subtraction as a method for artifact elimination. This method involves the creation of a template of the stimulation artifact from EEG signal recorded during non-invasive electrical stimulation with a sinusoidal alternating current. The present report describes results of the effects of a simple moving average filtration that varies based on averaging parameters; in particular, we varied the number of sinusoidal periods per segment of the recorded signal and the number of segments used to construct an artifact template. Given the ongoing lack of a mathematical model that allows for the prediction of the "hidden" EEG signal with the alternating current stimulation artifact, we propose performing an earlier simulation that is based on the addition of artificial stimulation artifact to the known EEG signal. This solution allows for the optimization of filtering parameters with detailed knowledge about the accuracy of artifact removal. The algorithm, designed in the MATLAB environment, has been tested on data recorded from two volunteers subjected to sinusoidal transorbital alternating current stimulation. Analysis of the percentage difference between the original and filtered signal in time and frequency domain highlights the advantage of 1-period filtration.

Cortical Inactivation Does Not Block Response Enhancement in the Superior Colliculus.

Repetitive visual stimulation is successfully used in a study on the visual evoked potential (VEP) plasticity in the visual system in mammals. Practicing visual tasks or repeated exposure to sensory stimuli can induce neuronal network changes in the cortical circuits and improve the perception of these stimuli. However, little is known about the effect of visual training at the subcortical level. In the present study, we extend the knowledge showing positive results of this training in the rat's Superior colliculus (SC). In electrophysiological experiments, we showed that a single training session lasting several hours induces a response enhancement both in the primary visual cortex (V1) and in the SC. Further, we tested if collicular responses will be enhanced without V1 input. For this reason, we inactivated the V1 by applying xylocaine solution onto the cortical surface during visual training. Our results revealed that SC's response enhancement was present even without V1 inputs and showed no difference in amplitude comparing to VEPs enhancement while the V1 was active. These data suggest that the visual system plasticity and facilitation can develop independently but simultaneously in different parts of the visual system.

Vision modulation, plasticity and restoration using non-invasive brain stimulation - An IFCN-sponsored review.

The visual system has one of the most complex structures of all sensory systems and is perhaps the most important sense for everyday life. Its functional organization was extensively studied for decades in animal and humans, for example by correlating circumscribed anatomical lesions in patients with the resulting visual dysfunction. During the past two decades, significant achievements were accomplished in characterizing and modulating visual information processing using non-invasive stimulation techniques of the normal and damaged human eye and brain. Techniques include transcranial magnetic stimulation (TMS) and low intensity electric stimulation using either direct or alternating currents applied transcranially (tDCS or tACS) near or above the visual cortex, or alternating currents applied transorbitally (trACS). In the case of transorbital stimulation of the visual system the electrodes are attached near the eye, to the eyelids (transpalpebral electrical stimulation - TPES) or the cornea (tanscorneal electrical stimulation TcES). Here, we summarize the state-of-the-art of visual system magnetic and electric stimulation as a method to modulate normal vision, induce brain plasticity, and to restore visual functions in patients. We review this field's history, models of current flow paths in the eye and brain, neurophysiological principles (e.g. entrainment and after-effects), the effects on vision in normal subjects and the clinical impact on plasticity and vision restoration in patients with low vision, with a particular focus on "off-line" or "after-effects". With regard to the therapeutic possibilities, ACS was demonstrated to be effective in patients affected by glaucoma and optic neuropathy, while tDCS and random noise stimulation (tRNS) are most promising for the treatment of amblyopia, hemianopia and myopia. In addition, rTMS applied above the occipital area is a promising approach to treat migraine, neglect and hemianopia. Although the response to these treatment options is better than to sham stimulation in double blinded clinical studies, the clinical efficacy is still rather variable and a proportion of patients do not respond. It is therefore imperative to better understand the mechanisms of action to be able to optimize treatment protocols possibly through personalization of brain stimulation protocols. By identifying the current opportunities and challenges in the field, we hope to provide insights to help improve neuromodulation protocols to restore visual function in patients with visual system damage.

Oscillations in Spontaneous and Visually Evoked Neuronal Activity in the Superficial Layers of the Cat's Superior Colliculus.

Oscillations are ubiquitous features of neuronal activity in sensory systems and are considered as a substrate for the integration of sensory information. Several studies have described oscillatory activity in the geniculate visual pathway, but little is known about this phenomenon in the extrageniculate visual pathway. We describe oscillations in evoked and background activity in the cat's superficial layers of the superior colliculus, a retinorecipient structure in the extrageniculate visual pathway. Extracellular single-unit activity was recorded during periods with and without visual stimulation under isoflurane anesthesia in the mixture of N2O/O2. Autocorrelation, FFT and renewal density analyses were used to detect and characterize oscillations in the neuronal activity. Oscillations were common in the background and stimulus-evoked activity. Frequency range of background oscillations spanned between 5 and 90 Hz. Oscillations in evoked activity were observed in about half of the cells and could appear in two forms -stimulus-phase-locked (10-100 Hz), and stimulus-phase-independent (8-100 Hz) oscillations. Stimulus-phase-independent and background oscillatory frequencies were very similar within activity of particular neurons suggesting that stimulus-phase-independent oscillations may be a form of enhanced "spontaneous" oscillations. Stimulus-phase-locked oscillations were present in responses to moving and flashing stimuli. In contrast to stimulus-phase-independent oscillations, the strength of stimulus-phase-locked oscillations was positively correlated with stimulus velocity and neuronal firing rate. Our results suggest that in the superficial layers of the superior colliculus stimulus-phase-independent oscillations may be generated by the same mechanism(s) that lie in the base of "spontaneous" oscillations, while stimulus-phase-locked oscillations may result from interactions within the intra-collicular network and/or from a phase reset of oscillations present in the background activity.

Specvis: Free and open-source software for visual field examination.

Visual field impairment affects more than 100 million people globally. However, due to the lack of the access to appropriate ophthalmic healthcare in undeveloped regions as a result of associated costs and expertise this number may be an underestimate. Improved access to affordable diagnostic software designed for visual field examination could slow the progression of diseases, such as glaucoma, allowing for early diagnosis and intervention. We have developed Specvis, a free and open-source application written in Java programming language that can run on any personal computer to meet this requirement (http://www.specvis.pl/). Specvis was tested on glaucomatous, retinitis pigmentosa and stroke patients and the results were compared to results using the Medmont M700 Automated Static Perimeter. The application was also tested for inter-test intrapersonal variability. The results from both validation studies indicated low inter-test intrapersonal variability, and suitable reliability for a fast and simple assessment of visual field impairment. Specvis easily identifies visual field areas of zero sensitivity and allows for evaluation of its levels throughout the visual field. Thus, Specvis is a new, reliable application that can be successfully used for visual field examination and can fill the gap between confrontation and perimetry tests. The main advantages of Specvis over existing methods are its availability (free), affordability (runs on any personal computer), and reliability (comparable to high-cost solutions).

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention.

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation.

Glaucoma -state of the art and perspectives on treatment.

Glaucoma is a chronic optic neuropathy characterized by progressive damage to the optic nerve, death of retinal ganglion cells and ultimately visual field loss. It is one of the leading causes of irreversible loss of vision worldwide. The most important trigger of glaucomatous damage is elevated eye pressure, and the current standard approach in glaucoma therapy is reduction of intraocular pressure (IOP). However, despite the use of effective medications or surgical treatment leading to lowering of IOP, progression of glaucomatous changes and loss of vision among patients with glaucoma is common. Therefore, it is critical to prevent vision loss through additional treatment. To implement such treatment(s), it is imperative to identify pathophysiological changes in glaucoma and develop therapeutic methods taking into account neuroprotection. Currently, there is no method of neuroprotection with long-term proven effectiveness in the treatment of glaucoma. Among the most promising molecules shown to protect the retina and optic nerve are neurotrophic factors. Thus, the current focus is on the development of safe and non-invasive methods for the long-term elevation of the intraocular level of neurotrophins through advanced gene therapy and topical eye treatment and on the search for selective agonists of neurotrophin receptors affording more efficient neuroprotection.

Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain.

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.

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.

Reciprocal inhibition and slow calcium decay in perigeniculate interneurons explain changes of spontaneous firing of thalamic cells caused by cortical inactivation.

The role of cortical feedback in the thalamocortical processing loop has been extensively investigated over the last decades. With an exception of several cases, these searches focused on the cortical feedback exerted onto thalamo-cortical relay (TC) cells of the dorsal lateral geniculate nucleus (LGN). In a previous, physiological study, we showed in the cat visual system that cessation of cortical input, despite decrease of spontaneous activity of TC cells, increased spontaneous firing of their recurrent inhibitory interneurons located in the perigeniculate nucleus (PGN). To identify mechanisms underlying such functional changes we conducted a modeling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered six network topologies of the retino-geniculo-cortical system. All models were robust against changes of axonal delays except for the delay between the LGN feed-forward interneuron and the TC cell. The best representation of physiological results was obtained with models containing reciprocally connected PGN cells driven by the cortex and with relatively slow decay of intracellular calcium. This strongly indicates that the thalamic reticular nucleus plays an essential role in the cortical influence over thalamo-cortical relay cells while the thalamic feed-forward interneurons are not essential in this process. Further, we suggest that the dependence of the activity of PGN cells on the rate of calcium removal can be one of the key factors determining individual cell response to elimination of cortical input.

Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients.

Spectral receptive field properties of visually active neurons in the caudate nucleus.

Recent studies stress the importance of the caudate nucleus in visual information processing. Although the processing of moving visual signals depends upon the capability of a system to integrate spatial and temporal information, no study has investigated the spectral receptive field organization of the caudate nucleus neurons yet. Therefore, we tested caudate neurons of the feline brain by extracellular single-cell recording applying drifting sinewave gratings of various spatial and temporal frequencies, and reconstructed their spectral receptive fields by plotting their responsiveness as a function of different combinations of spatial and temporal frequencies. The majority of the caudate cells (74%) exhibited peak tuning, which means that their spatio-temporal frequency response profile had a characteristic region of increased activity with a single maximum in the spatio-temporal frequency domain. In one-quarter of the recorded caudate neurons ridge tuning was found, where the region of increased activity, forming an elongated ridge of maximal sensitivity parallel or angled to the spatial or the temporal frequency axis, indicating temporal (16%), spatial (5%) or speed (5%) tuning, respectively. The velocity preference of the ridge tuned caudate nucleus neurons is significantly lower than that of the peak tuned neurons. The peak tuned neuron could encode high velocities, while the ridge tuned neurons were responsible for the detection of moderate and lower velocities. Based upon our results, we suggest that the wide variety of spatio-temporal frequency response profiles might represent different functional neuronal groups within the caudate nucleus that subserve different behaviors to meet various environmental requirements.

Variability of visual responses of superior colliculus neurons depends on stimulus velocity.

Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways.

Associative pairing involving monocular stimulation selectively mobilizes a subclass of GABAergic interneurons in the mouse visual cortex.

Levels of gamma-aminobutyric acid (GABA) and its synthesizing enzyme in cerebral cortex are regulated by sensory experience. Previously we found that associative pairing of vibrissae stimulation and tail shock results in upregulation of GABAergic markers in the mouse barrel cortex. In order to ascertain whether GABAergic upregulation also accompanies associative pairing in other sensory modalities, we examined the mouse visual cortex after analogous training with visual stimulus. During pairing, visual stimulus (CS) was coupled with a tail shock (UCS). We examined the density of cells expressing glutamic acid decarboxylase (GAD) and parvalbumin (PV) in monocular and binocular segments of the primary visual cortex (V1). The auditory cortex was used as a control. After monocular training, the density of cells expressing GAD rose significantly in the monocular segment of V1 contralateral to the stimulated eye, compared with the opposite hemisphere. This effect was due to the association of CS and UCS, as no changes were found after visual stimulation alone or in the auditory cortex. No changes were noted in the density of PV(+) neurons, so the effect was attributed to GAD(+)/PV(-) neurons. Mobilization of a specific subclass of GABAergic cells, observed after associative pairing in the somatosensory and visual cortices, may reflect the necessity to restrict the activity of circuits involved in sensory association.