COUDÉ G., MAROIS A., CASANOVA C. (2000) Effects of angiotensin II on visual evoked potentials in the superior colliculus of juvenile rats. Neuropeptides. 34: (in press).

There are age-related changes in the relative expression of the AT1 and AT2 receptors of angiotensin (Ang II) in brain regions such as the superior colliculus, a midbrain visual structure where both receptor subtypes are found. We investigated the effects of Ang II on gross visual activity in the colliculus of anesthetized rats aged between 15 and 35 post-natal days. Microinjection of Ang II in the superficial layers yielded a strong reduction in the amplitude of visual evoked potentials in a dose-related manner. Injection of the peptide in more ventral collicular layers did not modify the potential confirming the discrete localization of the angiotensinergic receptors in the superficial layers. Preliminary data indicated that the co-injection of Ang II with Losartan or PD 123319 yielded a partial blockade of Ang II suppressive effects, indicating that both AT1 and AT2 receptors are likely to be involved in mediating these responses. Overall, this study shows that the inhibitory nature of Ang II action is similar in juvenile and adult animals (Merabet et al. 1994 and Merabet et al. 1997).

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MERABET L., MINVILLE K., PTITO M., CASANOVA C. (2000) Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns.  Neuroscience. 97: 611-623.

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculo-striate and extra-geniculo-striate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) respond to the motion of a texture pattern with sustained discharges. Generally, responses to noise were more broadly tuned for direction compared to gratings, however direction selectivity appeared more pronounced in response to noise. The majority of cells were selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 deg/sec). Velocity tuning was comparable to that of its principle thalamic input, the lateral-posterior pulvinar nucleus. Generally, responsiveness of cells in posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis

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MERABET L., DESAUTELS A., MINVILLE K., CASANOVA C. (1998). Motion integration in a thalamic visual nucleus. Nature. 396: 265-268.

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.

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 MINVILLE K., CASANOVA C. (1998) Spatial frequency processing in PMLS cortex does not depend on the projections from the striate-recipient zone of the cat's lateral posterior-pulvinar complex. Neuroscience . 84: 699-711

It is generally considered that the posteromedial part of the cat?s lateral  suprasylvian (PMLS) cortex is involved in the analysis of image motion. The main afferents of the PMLS cortex come from a direct retino-geniculate  pathway and indirect retino-tectal and retino-geniculo-cortical pathways. Removal of the primary visual cortex does not affect the spatial and temporal  processing of PMLS cells suggesting that these properties are derived from thalamic input. We have investigated the possibility that the striate-recipient  zone (LPl) of the LP-pulvinar complex may be responsible for the spatial (and temporal) frequency processing in PMLS cortex since these two regions  establish strong bidirectional connections and share many visual properties. Experiments were done on anesthetized normal adult cats. Visual responses  in PMLS were recorded before, during, and after the deactivation of LPl accomplished by the injection of lidocaine or GABA. Results can be  summarized as follows. A total of 64 cells was tested. Out of this number, 11 units were affected by the deactivation of the lateral part of LP and one cell, by  the blockade of pulvinar. For all cells, except one, the effect consisted in a global reduction of the evoked discharge rate suggesting that the  thalamo-PMLS projections are excitatory in nature. We did not find any significant differences in the optimal spatial frequency, nor in the width of the  tuning function, whether the grating was presented at half- or saturation contrast. In addition, there were no significant differences between the low-  and high cut-off spatial frequency values computed before and after the deactivation of LPl. No specific changes were observed in the contrast  sensitivity function of the PMLS cells. Similar results were observed with respect to the temporal frequency tuning functions. Deactivating the LPl did  not modify the direction selectivity nor the organization of the subregions of the PMLS "classical" receptive fields.
The absence of strong changes in PMLS cell response properties following  the functional blockade of LPl suggests that the projections from this part of the thalamus are not essential to generate the spatial characteristics of most  PMLS receptive fields. These properties may be derived from other thalamic inputs (e.g., MIN) and/or from the intrinsic computation of the afferent signals  within the PMLS cortex. On the other hand, it is possible that the LPl-PMLS loop may be involved in other functions such as the analysis of complex  motion as suggested by the findings from our and other groups.

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MERABET L., De GASPARO M., CASANOVA C. (1997) Inhibitory effects  of angiotensin II on visual responses of the rat superior colliculus: AT1 and AT2 receptor contributions. Neuropeptides. 31: 5: 469-481.

Angiotensin II (Ang II) has traditionally been regarded as a peripherally circulating and acting hormone involved in fluid homeostasis and blood  pressure regulation. With the rather recent localization of Ang II receptors within the mammalian brain,  renewed interest has emerged in the hopes of  elucidating the central impact and function of this hormone. One region that has been clearly demonstrated to express Ang II receptors is the superior  colliculus (SC). This mesencephalic structure plays an important role in sensory visuomotor integration. Receptors for Ang II (of both the AT1 and AT2  subtypes) have been localized within the superficial layers of this structure, that is, the areas that are visually responsive. In the hope of characterising the  role of Ang II in the SC, we have attempted to physiologically activate these receptors in vivo and observe the effects of Ang II on visually evoked  responses. In the attempt to identify the receptor subtype(s) responsible in mediating these effects, Ang II was injected concomittantly with selective  receptor ligands. Experiments were performed on adult rats prepared in classical fashion for electrophysiological studies. Through micro injection of  Ang II, and the simultaneous recording of visually evoked potentials (VEP) to flash stimulation, we have observed that this peptide yields a strong  suppressive effect on visual neuronal activity. By injecting Ang II at various concentrations (10-3M to 10-10M), we have further observed that the effects  of this peptide express a dose related dependency. Injection of Ang II in progressively more ventral layers yielded less pronounced effects  demonstrating physiologically the discrete localization of these receptors in the stratum griseum superficiale (SGS). Co-injection of Ang II with Losartan  yielded a near complete blockade of Ang II suppressive effects, suggesting that AT1 receptors play a prominent role in mediating these responses.  However, co-injection of Ang II with PD 123319 yielded a slight, but yet significant partial blockade. Co-injection of Ang II with both the AT1 and AT2  receptor antagonists yielded a complete blockade of the Ang II effect. Finally, the AT2 receptor ligand CGP 42112 was shown to posses full agonist  properties. Taken together, these findings suggest that the AT1 receptor is predominately involved in mediating Ang II responses in the SC and there  appears to be some indication of AT2 receptor involvement as well. However, the underlying mechanisms (such as receptor interactions), the exact  specificity of the ligands used, and the possibility of other receptor subtype implication have yet to be explored fully.

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 BOUMGHAR L., MAROIS A., JOLICOEUR F., CASANOVA C. (1997) Effects of apomorphine on cell response in the lateral geniculate nucleus. Can. J. Physiol. Pharmacol.75: 853-858.

It has been shown that enhancing or reducing dopaminergic activity in the  retina modifies the balance between center and surround responses of retinal neurons such as ganglion cells. We investigated how these changes are  reflected in the dorsal lateral geniculate nucleus (dLGN) by studying the effects of injections of apomorphine, a mixed D1 and D2 agonist of dopamine  (DA), on the visual responses of geniculate cells. Experiments were carried out on anesthetized adult pigmented rabbits. A varnished tungsten  microelectrode was used to record single-unit activity in the dLGN. The flash ERG was also recorded to monitor retinal changes and to confirm the  success of the injections. Apomorphine was injected intravitreally or intravenously. The results can be summarized as follows. Apomorphine  decreased the amplitude of the b-wave of the ERG. For most dLGN cells, apomorphine produced a strong reduction in response amplitude evoked by  sine-wave grating stimuli, presented at various spatial frequencies. Responses to flashing spots were also reduced but to a much lesser extent  than those to gratings. In addition, the balance between the responses to small and large spots changed in favor of large stimuli. Consequently, after  injection of apomorphine, the geniculate cells were preferentially activated by large sized flashing stimuli. These data suggest that apomorphine can reduce  the spatial contrast sensitivity of cells in the dLGN. This effect could be mediated by the reduction of the strength of lateral inhibition at the retinal level.

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CASANOVA C., SAVARD T., DARVEAU S. (1997). Contribution of area 17 to cell response in the striate-recipient zone of the cat's lateral posterior-pulvinar complex. Eur. J. Neurosci. 9: 1026-1036.

The cat's lateral posterior-pulvinar complex (LP-pulvinar) contains three main  representations of the visual field. The lateral part of the LP nucleus (LPl or striate-recipient zone) is the only region of these extrageniculate nuclei which  receives afferents from the primary visual cortex. We have investigated the contribution of area 17 to the response properties (orientation and spatial  frequency tuning functions) of LPl neurons by cooling or lesioning the visual cortex. Responses of 40 LPl cells were studied before, during and after the  reversible cooling of the striate cortex. When tested for orientation, a total of 10 units out of 28 was affected (36%). For most of these cells (8 out of 10),  cooling the visual cortex yielded a reduction of the cells' visual responses without altering their orientation selectivity (there was no significant change of  the orientation tuning width). For only two cells, inactivation led to an increase of the response amplitude. Also, blocking the visual cortex never modified the  direction selectivity of LPl cells. When tested for spatial frequency, 12 neurons out of 33 were affected (36%) by the experimental protocol. In most cases, we  observed a reduction of the responses at each spatial frequency tested, with no change in tuning bandwidth. For only three LPl cells, the effects of  inactivation of the visual cortex were restricted to specific spatial frequencies, altering the profile of the spatial frequency tuning function. In 5 cats, removing  area 17 reduced the proportion of visual neurons in LPl and the spared visually evoked responses were noticeably depressed. Despite the reduction  of responsiveness, a few LPl receptive fields within the cortical scotoma were still sensitive to the orientation and/or direction of a moving stimulus. This last  observation suggests that some properties in LPl could be generated either by circuits intrinsic to the LPl or by afferents from extrastriate cortical areas.  Overall, these results indicate that projections from the visual cortex to the striate-recipient zone of the LP-pulvinar complex are mainly excitatory.  Despite the strong impact of the area 17 projections, our data suggest that the extrastriate cortex could also play a role in the establishement of response properties in the cat's LPl.

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CHORVATOVA A., GALLO-PAYET N., CASANOVA C., PAYET M.D. (1996). Modulation of membrane potential and ionic currents by the AT1 and AT2 receptors of angiotensine II. Cell. Signal. 8: 525-532.

Angiotensin II, the principal effector of the renin-angiotensin system,  modulates various ionic currents. Its effects on potassium currents, including outward transient potassium current, the inward or outward rectifiers, as well  as Ca2+-activated potassium currents, is well described. Other ionic currents, such as voltage-dependent calcium currents, cationic or chloride currents, are  also altered by the hormone. All these effects provoke changes in membrane potential, such as modulation of action potentials firing or resting membrane  potential and control intracellular calcium concentration. Summarized here are the results obtained on these membrane electrical properties using electrophysiological recordings.

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CASANOVA C., SAVARD T. (1996). Responses of cells in the striate-recipient zone of the cat's LP-pulvinar complex to moving texture patterns. Neuroscience . 70, 439-447.

We have studied the response properties of cells in the striate-recipient zone  (LPl) of the LP-pulvinar complex to the motion of textured patterns [visual noise]. Our purpose was to determine basic noise response characteristics  and to compare these properties to that of cells in area 17 known to project to the LPl. Practically all LPl cells (87%) responded to the motion of visual noise.  The evoked discharges were either sustained or characterized by several bursts. On average, as found in cortex, LPl neurons were more broadly tuned  for the direction of noise than that of gratings (bandwidths of 49 and 36 deg, respectively ; t test, p<0.005). Noise tuning function in LPl was comparable to  that found in cortex (mean of 48 deg). One third of the LPl units did not exhibit any preferences for drift direction of noise. Such cells were virtually not  encountered in the striate cortex. This group of LPl cells was generally not tuned for grating direction. For practically all LPl cells, responses to noise  varied as a function of drift velocity. The mean optimal velocity was 27.5 deg/sec with mean bandwidth of 2.5 octaves. LPl cells were sensitive to a  broader range of velocities  than complex cells in area 17. The results of the present study showed that visual noise is an appropriate stimulus for studying  motion sensitivity of cells in the LPl. It also revealed that the noise response properties, such as direction and velocity tuning functions, are very similar to  those reported in the striate cortex. The exact contribution of area 17 in the visual noise responsiveness of LPl cells remains to be determined. This study  provides additional evidence that the LP-pulvinar complex may be involved in many aspects of visual processing.

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 CASANOVA C., SAVARD T. (1996). Motion sensitivity and stimulus interactions in the striate-recipient zone of the lateral posterior-pulvinar complex. Prog. Brain Res. 112: 277-287.

The cat's lateral posterior-pulvinar complex (LP-pulvinar) establishes  reciprocal connections with the anterior ectosylvian visual (AEV) and lateral suprasylvian (LS) cortices; two regions which are believed to be involved in  motion analysis. We have investigated the motion sensitivity of neurons in the LP-pulvinar complex by 1) studying the response properties of cells in the  striate-recipient zone of the LP nucleus (LPl) to the drift of a two-dimensional texture pattern (visual noise) and 2) determining the extent to which the latter  stimulus can modify the spatial frequency tuning function of LPl cells. Experiments were carried out on anesthetized normal adult cats. Almost all  LPl cells (55 out of 63, 87%) responded to the motion of visual noise. For most units (39 out of 55, 71%), responses varied as a function of the direction  of motion (bandwidth of 49 deg). One third of the LPl units did not exhibit any preference for drift direction of noise. For practically all LPl cells, responses to  noise varied as a function of drift velocity. Optimal velocities were distributed from 2 to 35o/sec with a mean value of 27.5 o/sec (mean bandwidth of 2.5  octaves). The influence of visual noise on the spatial frequency tuning function of 22 LPl cells was also studied. For half of LPl cells, responses at all spatial  frequencies were reduced when the grating and the texture pattern were moving in opposite directions (anti phase condition). This masking effect of  noise was rarely observed when both stimuli were drifted in the same direction (in phase condition). These results suggest that the LP-pulvinar  complex may be part of extrageniculate pathways involved in the analysis of motion of visual targets and/or the analysis of the relative movement between an object and its surrounding environment.

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CASANOVA C., SAVARD T., NORDMANN J.P., MOLOTCHNIKOFF S., MINVILLE K. (1995). Comparison of the responses to moving texture  patterns of simple and complex cells in the cat's area 17. J. Neurophysiol. 74:  1271-1286.

     1. Whether complex (C) cells are the only truly texture-sensitive units in the cat's primary visual cortex remains controversial. In view of the strong  physiological significance of having putatively only one class of cells sensitive to visual noise in the striate cortex, we reinvestigated this issue. Sensitivities  of  simple (S) and C cells  to noise were quantitatively studied and compared in order to clearly document the response properties of cells in the striate  cortex to visual noise and to establish whether one can unequivocally segregate S from C cells based on those specific properties.
    2. Receptive fields were stimulated with all relevant stimuli i.e., drifting sine-wave gratings, electronically generated noise pattern of 256 x 256  elements (ratio 1:1 of dark and light elements), and flashing and moving bars (both bright and dark).
    3. A total of  60 S cells out of 85 (70.6%) and 90 C cells out of 101 (81.8%)  responded to the motion of visual noise. Responses of most C cells were sustained i.e. their discharge rate was maintained at a constant level  throughout presentation of the stimulus. On the other hand, responses of the majority of S cells were characterized by several bursts of discharges. On  average, optimal firing rates were greater for gratings than for noise.
    4. For practically all cells, responses to noise varied as a function of  direction of motion. The mean direction bandwidths were respectively 43 ± 24o and 48 ±  23o for S and C cells. In both groups, neurons were more  broadly tuned for the direction of noise than that of gratings (t test, p<0.001).  We rarely observed bimodal tuning curves for noise, with each peak lying on  either side of the orientation curve. These results could be expected if one considers texture stimuli not in the space domain [as dot patterns] but in the  frequency domain, i.e., patterns containing all spatial frequencies and orientations.
    5. In general, the direction indices of S and C cells were similar whether  they were stimulated by drifting noise or gratings. S cells had a slight tendency to be more direction selective for noise than for gratings.
    6. For all S and C cells tested, responses to noise varied as a function of drift velocity. The mean optimal velocity was 12.9 and 10.2o/sec for S and C  cells respectively (t test, >0.05). Most cells were bandpass with mean bandwidths of 2.2 and 2.7 octaves for S and C cells, respectively. Enlarging  the size of pattern elements yielded an increase in response amplitude and bandwidth in both cell groups.
    7. Texture-sensitive units were distributed in all layers. Strong  texture-sensitive C cells were generally located in the infragranular layers. There was no clear relationship between laminar distribution and noise responsiveness for S cells.
    8. Our study shows that, except for response profile and strength, there were no significant differences between response properties of S and C cells  with respect to their noise sensitivity. These data suggest that visual noise does not allow one to clearly segregate S from C cells. Also, they do not  support the notion that C cells receive inputs not mediated by S cells.

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MERABET  L., DeGASPARO M., CASANOVA C. (1994).  Neuromodulatory effects of Angiotensin II in the visual layers of the rat superior colliculus. Neuroreport 5: 2649- 2652.
 Recent autoradiographic studies have revealed the presence of both AT1 and AT2Angiotensin II (AngII) receptor subtypes in the superficial layers of the rat  superior colliculus (SC). We have investigated the effects of activating these receptors on visually evoked potentials (VEP) in the SC of adult rats. A  recording-injecting microelectrode filled with AngII was lowered into the superficial layers of the SC. AngII was injected at concentrations varying from  10-4 to 10-10M. Injection of the peptide yielded a reduction in the amplitude of the VEP. This reduction usually occurred within 2 to 3 min following AngII  injection with a 50% recovery of most of the signal 20 to 30 min thereafter. AngII did not modify the signal when injected in collicular layers ventral to the  stratum opticum. Furthermore, concomitant injection of AngII with the specific AT1 receptor antagonist Losartan failed to reduce the evoked response  suggesting that the effects of AngII in the SC are likely mediated by AT1 receptors.

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