Christian Casanova

Motion integration in a thalamic visual nucleus

Thalamic nuclei have long been regarded as passive relay stations for sensory information en route to higher level processing in the cerebral cortex. Recently, physiological and theoretical studies have reassessed the role of the thalamus and it has been proposed that thalamic nuclei may actively participate with cortical areas in processing specific information. In support of this idea, we now show that a subset of neurons in an extrageniculate visual nucleus, the lateral-posterior pulvinar complex, can signal the true direction of motion of a plaid pattern, indicating that thalamic cells can integrate different motion signals into a coherent moving percept. This is the first time that these computations have been found to occur outside the higher-order cortical areas,,,. Our findings implicate extrageniculate cortico–thalamo–cortical loops in the dynamic processing of image motion, and, more generally, as basic computational modules involved in analysing specific features of complex visual scenes.

Real-time diffuse optical tomography based on structured illumination

A new optical acquisition scheme based on a pair of digital micromirror devices is developed and applied to three-dimensional tomographic imaging of turbid media. By using pairs of illumination-detection patterns with a single detector, we were able to perform high-resolution quantitative volumetric imaging of absorption heterogeneities embedded in optically thick samples. Additionally, a tomographic reconstruction algorithm was implemented on a graphical processor unit to provide optical reconstructions at a frame rate of 2 Hz. The structured illumination method proposed in this work has significant cost advantages over camera systems, as only a single detector is required. This configuration also has the potential to increase frame rate.

On the use of isoflurane versus halothane in the study of visual response properties of single cells in the primary visual cortex

Halothane is a widely used anesthetic in research. It produces several alterations in organs, especially in the brain. Recently, isoflurane emerged in neuroscience laboratories. For many reasons it appears to be better than halothane for animal brain research (e.g. isoflurane induces lower intracranial pressure, and is less detrimental on the cardiovascular system). However, no one is in a position to recommend it in electrophysiology research because its effects on specific brain functions are relatively unknown. Given that both anesthetics yield different actions on gross brain activity (EEG, VEP), it is likely that they differentially affect single neuron activity. The goal of this study is to determine whether halothane or isoflurane use is best suited to study the receptive field properties of neurons in the cats primary visual cortex. Extra-cellular recordings were made for both anesthetics in area 17 of adult cats under different levels of anesthesia. Results indicate that various cell parameters differ under halothane anesthesia when compared with isoflurane. The main difference between the two anesthetics is the greater depression of the cell optimal visual response amplitude induced by isoflurane at equipotent concentration. Due to its stronger depressive effects, isoflurane may not be the ideal anesthetic for single-cell recordings in the primary visual cortex.

Structural and functional neuroprotection in glaucoma: role of galantamine-mediated activation of muscarinic acetylcholine receptors

Glaucoma is the leading cause of irreversible blindness worldwide. Loss of vision due to glaucoma is caused by the selective death of retinal ganglion cells (RGCs). Treatments for glaucoma, limited to drugs or surgery to lower intraocular pressure (IOP), are insufficient. Therefore, a pressing medical need exists for more effective therapies to prevent vision loss in glaucoma patients. In this in vivo study, we demonstrate that systemic administration of galantamine, an acetylcholinesterase inhibitor, promotes protection of RGC soma and axons in a rat glaucoma model. Functional deficits caused by high IOP, assessed by recording visual evoked potentials from the superior colliculus, were improved by galantamine. These effects were not related to a reduction in IOP because galantamine did not change the pressure in glaucomatous eyes and it promoted neuronal survival after optic nerve axotomy, a pressure-independent model of RGC death. Importantly, we demonstrate that galantamine-induced ganglion cell survival occurred by activation of types M1 and M4 muscarinic acetylcholine receptors, while nicotinic receptors were not involved. These data provide the first evidence of the clinical potential of galantamine as neuroprotectant for glaucoma and other optic neuropathies, and identify muscarinic receptors as potential therapeutic targets for preventing vision loss in these blinding diseases.

Chapter 28 When the auditory cortex turns visual

Abstract We studied visually guided behavior and the visual response properties of single auditory cortex (A1) neurons in neonatally operated hamsters with surgically induced, permanent, ectopic retinal projections to auditory thalamic nuclei and to visual thalamic nuclei which normally receive little direct retinal input. The surgically induced retino-thalamo-cortical pathways can mediate visual guided behaviors whose normal substrate, the pathway from the retina to the primary visual cortex via the primary thalamic visual nucleus, is missing. The visually evoked response properties of A1 neurons resemble in many respects those of neurons in V1 of normal hamsters: many A1 neurons have well-defined visual reseptive fields and preferences for orientation or direction of movement. In addition, some visually responsive cells in A1 are bimodal — they also respond to auditory stimuli. The visually responsive neurons in A1 probably account for the capacity of the auditory cortex to mediate visual behavior in ‘rewired hamsters’.

Roles of cannabinoid receptors type 1 and 2 on the retinal function of adult mice.

PURPOSE Endocannabinoids are important modulators of synaptic transmission and plasticity throughout the central nervous system. The cannabinoid receptor type 1 (CB1R) is extensively expressed in the adult retina of rodents, while CB2R mRNA and protein expression have been only recently demonstrated in retinal tissue. The activation of cannabinoid receptors modulates neurotransmitter release from photoreceptors and could also affect bipolar cell synaptic release. However, the impact of CB1R and CB2R on the retinal function as a whole is currently unknown. METHODS In the present study, we investigated the function of cannabinoid receptors in the retina by recording electroretinographic responses (ERGs) from mice lacking either CB1 or CB2 receptors (cnr1(-/-) and cnr2(-/-), respectively). We also documented the precise distribution of CB2R by immunohistochemistry. RESULTS Our results showed that CB2R is localized in cone and rod photoreceptors, horizontal cells, some amacrine cells, and bipolar and ganglion cells. In scotopic conditions, the amplitudes of the a-wave of the ERG were increased in cnr2(-/-) mice, while they remained unchanged in cnr1(-/-) mice. The analysis of the velocity-time profile of the a-wave revealed that the increased amplitude was due to a slower deceleration rather than an increase in acceleration of the waveform. Under photopic conditions, b-wave amplitudes of cnr2(-/-) mice required more light adaptation time to reach stable values. No effects were observed in cnr1(-/-) mice. CONCLUSIONS The data indicated that CB2R is likely to be involved in shaping retinal responses to light and suggest that CB1 and CB2 receptors could have different roles in visual processing.

Chapter 5 Higher-order motion processing in the pulvinar

Thalamic nuclei have long been considered as passive relay stations for sensory signals en route to the cerebral cortex, where higher level processing occurs. In recent years, it has been proposed that thalamic nuclei may actively participate in the processing of specific information in conjunction with cortical areas. In support of this hypothesis, we recently discovered that neurons in the main extrageniculate visual nucleus, the pulvinar, exhibit higher-order visual properties that were, until now, only associated with higher-order cortical areas. Pulvinar neurons can indeed code the veridical direction of a moving plaid pattern, indicating that these cells can integrate ambiguous signals into a coherent percept. This finding as well as our demonstration that there are cortico-thalamo-cortical loops involved in complex motion analysis open promising avenues in unraveling the function of the pulvinar complex in normal vision.

Evaluation of the specificity of antibodies raised against cannabinoid receptor type 2 in the mouse retina

Cannabinoid receptors (CB1R and CB2R) are among the most abundant G protein-coupled receptors in the central nervous system. The endocannabinoid system is an attractive therapeutic target for immune system modulation and peripheral pain management. While CB1R is distributed in the nervous system, CB2R has traditionally been associated to the immune system. This dogma is currently a subject of debate since the discovery of CB2R expression in neurons using antibody-based methods. The localization of CB2R in the central nervous system (CNS) could have a significant impact on drug development because it would mean that in addition to its effects on the peripheral pain pathway, CB2R could also mediate some central effects of cannabinoids. In an attempt to clarify the debate over CB2R expression in the CNS, we tested several commercially or academically produced CB2R antibodies using Western blot and immunohistochemistry on retinal tissue obtained from wild-type mice and mice lacking CB2R (cnr2−/−). One of the antibodies tested exhibited a valuable specificity as it marked a single band near the predicted molecular weight in Western blot and produced no staining in cnr2−/− mice retina sections. The other antibodies tested detected multiple bands in Western blot and labeled unidentified proteins when used with their immunizing peptide or on cnr2−/− retinal sections. We conclude that many commonly used antibodies raised against CB2R are not specific for use in immunohistochemistry, at least in the context of the mouse retina. Moreover, some of them tested presented significant lot-to-lot variability. Hence, caution should be used when interpreting prior and future studies using CB2R antibodies.

Cannabinoid receptor type 1 expression during postnatal development of the rat retina

Cannabinoid receptor type 1 (CB1R) participates in developmental processes in the central nervous system (CNS). The rodent retina represents an interesting and valuable model for studying CNS development, because it contains well‐identified cell types with clearly established and distinct developmental timelines. Very little is known about the distribution or function of CB1R in the developing retina. In this study, we investigated the expression pattern of CB1R in the rat retina during all stages of postnatal development. Western blots were performed on retinal tissue at different time points between P1 and adulthood. In order to identify the cells expressing the receptor and the age at which this expression started, immunohistochemical co‐staining was carried out for CB1R and markers of the different cell types comprising the retina. CB1R was already present at P1 in various cell types, i.e., ganglion, amacrine, horizontal, and mitotic cells. In the course of development, it appeared in cone photoreceptors and bipolar cells. For some cell types (bipolar, Müller, and some amacrine cells), CB1R was transiently expressed, suggesting a potential role of this receptor in developmental processes, such as migration, morphological changes, sub‐identity acquisition, and patterned retinal spontaneous activity. Our results also indicated that CB1R is largely expressed in the adult retina (cone photoreceptors and horizontal, most amacrine, and retinal ganglion cells), and may therefore contribute to retinal functions. Overall these results indicate that, as shown in other structures of the brain, CB1R could play an instrumental role in the development and function of the retina. J. Comp. Neurol. 519:1258–1280, 2011.

Abnormal cortical processing of pattern motion in amblyopia: evidence from fMRI.

Converging evidence from human psychophysics and animal neurophysiology indicates that amblyopia is associated with abnormal function of area MT, a motion sensitive region of the extrastriate visual cortex. In this context, the recent finding that amblyopic eyes mediate normal perception of dynamic plaid stimuli was surprising, as neural processing and perception of plaids has been closely linked to MT function. One intriguing potential explanation for this discrepancy is that the amblyopic eye recruits alternative visual brain areas to support plaid perception. This is the hypothesis that we tested. We used functional magnetic resonance imaging (fMRI) to measure the response of the amblyopic visual cortex and thalamus to incoherent and coherent motion of plaid stimuli that were perceived normally by the amblyopic eye. We found a different pattern of responses within the visual cortex when plaids were viewed by amblyopic as opposed to non-amblyopic eyes. The non-amblyopic eyes of amblyopes and control eyes differentially activated the hMT+ complex when viewing incoherent vs. coherent plaid motion, consistent with the notion that this region is centrally involved in plaid perception. However, for amblyopic eye viewing, hMT+ activation did not vary reliably with motion type. In a sub-set of our participants with amblyopia we were able to localize MT and MST within the larger hMT+ complex and found a lack of plaid motion selectivity in both sub-regions. The response of the pulvinar and ventral V3 to plaid stimuli also differed under amblyopic vs. non-amblyopic eye viewing conditions, however the response of these areas did vary according to motion type. These results indicate that while the perception of the plaid stimuli was constant for both amblyopic and non-amblyopic viewing, the network of neural areas that supported this perception was different.