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Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have shown a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. In this study, we studied the phenotype of maLPA1-null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor co-ordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes and co-ordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. [ABSTRACT FROM AUTHOR]

Purpose To show the visual capacity in two different albino mice (NMRI and CD1). Methods 66 albino mice from two mice's strains were analyzed: CD1 and NMRI, obtained about from two different organizations. Full field Electroretinogram was used in the functional analysis. The recommendation of the International Society for the Clinical Electrophysiology of Vision (ISCEV) was followed. Furthermore, we recorded ERG responses at chromatic sensitivity. We have compared immunohistoquimical photoreceptor's stain with arrestin, rodopsin, S‐opsin and M‐opsin. We have used antibodies anti‐achromatopsia gens, like GNTA2 and CNGB3. Results CD1 and NMRI electroretinogram results showed two different visual patrons: a normal responses and coneless vision. An important per cent of CD1 mice (≅ 30%) and NMRI mice (≅ 20%) have visual defects in the photopic responses. The affected mice show a very significant reduction on the cone responses (p<0,01). Because we used chromatic stimulus we can say that the photopic defect occur in every cone, we can appreciate colorblindness. The structural study allows us to say how the photoreceptors are affected when the electroretinogam photopic response is not adequate. The functional and cellular results seem to indicate that these mice suffer an achromatopsia. Conclusion Our experiments show the significant number of coneless mice in a normal order of the experimental animals. Ignorance of visual problems in experimental animals might compromise the results of conductual experiment or other kinds of studies. Electroretinogram tests are recommended before conductual studies with albino mice or different works, to know if the mice have a correct vision. [ABSTRACT FROM AUTHOR]

Purpose To study the variations in the circadian activity in the mouse behaviour with different composition of the luminous spectra. Blue light has been identified as one cause of retinal damage. Nevertheless, these wavelengths (400‐500nm) are important in the process of intrinsically photosensitive ganglion cells (ipRGCs) activation. These cells are essential in not forming images processes such as the pupillary reflex, regulation of the circadian activity and/or release of melatonin. Further, ipRGCs are necessary and sufficient to maintain the synchronization of endogenous cycles with circadian activity of each individual. Methods By using Circadian Activity cages and different mouse models, we have investigated their behaviour when exposed to the entire light spectrum or to different amounts of the light‐filtered blue component. We have analyzed the behaviour of C57BL6J mice, which have all retinal photosensitive cells, and Rd10 mice, who comprise ipRGCs as the only photosensitive cells in their retinas by postnatal day 100. Results The use of diverse mouse models has allowed us to investigate the contribution of different photoreceptor classes to the regulation of circadian activity in distinct light conditions. We have observed that ipRGCs are sufficient to maintain the synchronization of endogenous cycles with circadian activity of each individual. Mouse behaviour changes depending on the amount of blue light. Conclusion The maximum activation of melanopsin‐expressing cells is conditioned by the presence of filters for wavelengths below 500nm. Variations in behaviour exist depending on the amount of visible blue light filtered. [ABSTRACT FROM AUTHOR]

Purpose To study the mechanisms regulating specific protein expression throughout the circadian cycle in the mouse retina. In mammals, circadian rhythms are synchronized to light‐dark cycles via a photic input from the eyes. It is now clear that, besides rods and cones, a third class of photoreceptor exists in the mammalian retina: ipRGCs. These are known to regulate circadian entrainment and other non‐visual responses to light. A way of regulating PKC activity is compartmentalization inside retinal cells, which allows phosphorylation of its targets. Though this change of location is light dependent, it is unknown whether the sole presence of ipRGCs is sufficient to regulate it Methods Retinal sections from mice sacrificed at different times of day (ZT0,6,12,18) were immunostained for PKC. Immunoreactivity was analyzed in the soma and the axon terminal of PKC positive cells. The expression and sub‐cellular localization of PKC was studied by Western blotting of plasma membrane and cytosolic fractions, from retinas of mice containing all photoreceptors (C57) and mice lacking rods and cones (rd10). Furthermore, the expression pattern of the Na‐K‐2Cl cotransporter (NKCC1) was also tested, since NKCC1 could have a role in the regulation of PKC function Results The use of different mouse models has allowed us to investigate the contribution of different photoreceptor types to the to αPKC circadian regulation. Light induces αPKC expression and transport to the membrane compartment and this effect is mediated by both, classical photoreceptors and ipRGCs Conclusion ipRGCs, as well as classical photoreceptors, mediate changes in retinal protein expression throughout the circadian cycle [ABSTRACT FROM AUTHOR]

Aging contributes to the appearance of several retinopathies and is the largest risk factor for aged-related macular degeneration, major cause of blindness in the elderly population. Accumulation of undegraded material as lipofuscin represents a hallmark in many pathologies of the aged eye. Autophagy is a highly conserved intracellular degradative pathway that plays a critical role in the removal of damaged cell components to maintain the cellular homeostasis. A decrease in autophagic activity with age observed in many tissues has been proposed to contribute to the aggravation of age-related diseases. However, the participation of different autophagic pathways to the retina physiopathology remains unknown. Here, we describe a marked reduction in macroautophagic activity in the retina with age, which coincides with an increase in chaperone-mediated autophagy (CMA). This increase in CMA is also observed during retinal neurodegeneration in the Atg5(flox/flox) ; nestin-Cre mice, a mouse model with downregulation of macroautophagy in neuronal precursors. In contrast to other cell types, this autophagic cross talk in retinal cells is not bi-directional and CMA inhibition renders cone photoreceptor very sensitive to stress. Temporal and cell-type-specific differences in the balance between autophagic pathways may be responsible for the specific pattern of visual loss that occurs with aging. Our results show for the first time a cross talk of different lysosomal proteolytic systems in the retina during normal aging and may help the development of new therapeutic intervention for age-dependent retinal diseases., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)

It has been reported that section of the optic nerve in mammals causes death in >90% of the retinal ganglion cells (RGCs). The cells which survive the section experience an irreparable loss of many of their dendritic segments and a rapid retraction of the dendritic tree. However, some growth cones and abnormal processes have been also reported. Our aim was to make a quantitative study of the morphological changes found in rabbit RGCs after optic nerve section. The morphometrical analysis of the RGCs which survived the axotomy showed an increase in the diameter of the soma and a significant increase in the area of the dendritic field; also, the length of the dendritic segments was significantly longer in axotomized RGCs than in control cells. Terminal dendritic segments (T) and preterminal segments (PT) were both measured in control and axotomized cells; the length ratio of T : PT segments was significantly greater in the axotomized cells than in the controls. We conclude that RGCs which survived the axotomy experienced a significant growth of their terminal dendritic branches.

With the use of the whole-cell voltage-clamp technique, we have recorded the currents induced by ionotropic glutamate receptor agonists on isolated axonless horizontal cells (HC) of rabbit retina. Bath application of the non-N-methyl-D-aspartate receptor agonists: kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and L-glutamate (GLU) produced an increase in the conductance for non-selective cations. All the isolated horizontal cells responded to GLU, AMPA and KA. Responses elicited by GLU and AMPA but not KA exhibited a concentration-dependent desensitization. Application of N-methyl-D-aspartate (NMDA) evoked no responses. The rank order affinities of the agonists as estimated from EC50 values were AMPA > GLU > KA. Whereas KA had the lowest affinity of the agonists tested, it produced the largest currents. Hill coefficients of the concentration-response data were near 1 for AMPA, and 2 for KA and GLU. Coapplication of AMPA with cyclothiazide (CTZ) blocks AMPA receptor desensitization, and enhanced its effects on conductance. However, CTZ did not change the KA -induced conductances. In all cells tested, 6,7-dinitroquinoxaline (DNQX) completely and reversibly blocked the effects of KA and AMPA. The KA- and AMPA-induced currents were also completely blocked by 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a selective AMPA receptor antagonist. These results indicate that the responses to glutamate agonists in HC were mediated almost exclusively by AMPA receptors. Our study indicates that AMPA receptors play a fundamental role in mediating the synaptic input into rabbit horizontal cells.

In the vertebrate retina, the bipolar cell makes reciprocal synapses with amacrine cells at the axon terminal. It has been postulated that amacrine cells may control the transmitter release from bipolar cells by modulating their calcium currents (ICa). To clarify this possibility calcium currents were studied in bipolar cells of the mouse retina using a slice preparation. ICa was identified by voltage clamp protocols, ionic substitution and pharmacological tools. Depolarization to -30 mV from a holding voltage of -80 mV induced an inward current consisting of an initial transient and a long-lasting sustained component. The transient component was inactivated by holding the membrane at more positive voltages. Addition of 100 microM nifedipine suppressed the sustained component, leaving the transient component almost intact. The sustained component was enhanced when external solution contained 0.1 microM Bay K 8644 or when the external Ca2+ was substituted by equimolar Ba2+. Omega-conotoxin (10 microM omega-ctxn GVIA) did not alter either component. We concluded that the transient component is a low-voltage activated T-type ICa, while the sustained component is a high-voltage activated L-type ICa. T-type ICa was recorded in all cells tested, while L-type ICa was found only in cells that retained axon terminals ramifying in the inner plexiform layer. Thus, it is highly likely that L-type ICa is generated at the axon terminal and contributes to the transmitter release from the bipolar cell. The present results confirm that in addition to the T-type ICa that had been previously described, bipolar cells of the mammalian retina also contain L-type ICa similar to the one that has been reported in bipolar cells of the goldfish. The use of retinal slice preparation allowed us to record this current that was not seen previously in the dissociated mouse bipolar cells.