Lister Hooded Research Articles

Developmental trajectory of episodic-like memory in rats.

Episodic memory formation requires the binding of multiple associations to a coherent episodic representation, with rich detail of times, places, and contextual information. During postnatal development, the ability to recall episodic memories emerges later than other types of memory such as object recognition. However, the precise developmental trajectory of episodic memory, from weaning to adulthood has not yet been established in rats. Spontaneous object exploration tasks do not require training, and allow repeated testing of subjects, provided novel objects are used on each trial. Therefore, these tasks are ideally suited for the study of the ontogeny of episodic memory and its constituents (e.g., object, spatial, and contextual memory). In the present study, we used four spontaneous short-term object exploration tasks over two days: object (OR), object-context (OCR), object-place (OPR), and object-place-context (OPCR) recognition to characterise the ontogeny of episodic-like memory and its components in three commonly used outbred rat strains (Lister Hooded, Long Evans Hooded, and Sprague Dawley). In longitudinal studies starting at 3-4 weeks of age, we observed that short term memory for objects was already present at the earliest time point we tested, indicating that it is established before the end of the third week of life (consistent with several other reports). Object-context memory developed during the fifth week of life, while both object-in-place and the episodic-like object-place-context memory developed around the seventh postnatal week. To control for the effects of previous experience in the development of associative memory, we confirmed these developmental trajectories using a cross-sectional protocol. Our work provides robust evidence for different developmental trajectories of recognition memory in rats depending on the content and/or complexity of the associations and emphasises the utility of spontaneous object exploration tasks to assess the ontogeny of memory systems with high temporal resolution.

Rearing in an Enriched Environment Ameliorates the ADHD-like Behaviors of Lister Hooded Rats While Suppressing Neuronal Activities in the Medial Prefrontal Cortex.

In addition to genetic factors, environmental factors play a role in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). This study used Lister hooded rats (LHRs) as ADHD model animals to evaluate the effects of environmental factors. Male LHR pups were kept in four rearing conditions from postnatal day 23 (4 rats in a standard cage; 12 rats in a large flat cage; and 4 or 12 rats in an enriched environment [EE]) until 9 weeks of age. EE rearing but not rearing in a large flat cage decreased the activity of LHRs in the open field test that was conducted for 7 consecutive days. In the drop test, most rats reared in an EE remained on a disk at a height, whereas most rats reared in a standard cage fell off. RNA sequencing revealed that the immediate-early gene expression in the medial prefrontal cortex of LHRs reared in an EE was reduced. cFos-expressing neurons were reduced in number in LHRs reared in an EE. These results suggest that growing in an EE improves ADHD-like behaviors and that said improvement is due to the suppression of neuronal activity in the mPFC.

Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders.

PurposeTo evaluate the therapeutic benefit of a novel peptide, ALM201, in ocular pathologic vascularization.DesignExperimental study in mouse, rat, and rabbit animal models.ParticipantsTen-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits.MethodsCorneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration.Main Outcome MeasuresClinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments.ResultsAssessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm2 vs. 1837 ± 195.9 cells/mm2, respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm3 vs. 187,923 ± 28,575 μm3; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle.ConclusionsALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.

Lack of general learning ability factor in a rat test battery measuring a wide spectrum of cognitive domains.

Objective: In the framework of a larger project aiming to test putative cognitive enhancer drugs in a system with improved translational validity, we established a rodent test battery, where different, clinically relevant cognitive domains were investigated in the same animal population. The aim of the current study was to check whether performances in the different tasks representing different cognitive functions are assay-specific or may originate in an underlying general learning ability factor. Methods: In the experiments 36 Long-Evans and 36 Lister Hooded rats were used. The test battery covered the following cognitive domains: attention and impulsivity (measured in the 5-choice serial reaction time task), spatial memory (Morris water-maze), social cognition (cooperation task), cognitive flexibility (attentional set shifting test), recognition memory (novel object recognition) and episodic memory (water-maze based assay). The outcome variables were analyzed by correlation analysis and principal component analysis (PCA). The datasets consisted of variables measuring learning speed and performance in the paradigms. From the raw variables composite variables were created for each assay, then from these variables a composite score was calculated describing the overall performance of each individual in the test battery. Results: Correlations were only found among the raw variables characterizing the same assay but not among variables belonging to different tests or among the composite variables. The PCAs did not reduce the dimensionality of the raw or composite datasets. Graphical analysis showed variable performance of the animals in the applied tests. Conclusions: The results suggests the assay outcomes (learning performance) in the system are based on independent cognitive domains.

Strain Comparison in Rats Differentiates Strain-Specific from More General Correlates of Noise-Induced Hearing Loss and Tinnitus

Experiments in rodent animal models help to reveal the characteristics and underlying mechanisms of pathologies related to hearing loss such as tinnitus or hyperacusis. However, a reliable understanding is still lacking. Here, four different rat strains (Sprague Dawley, Wistar, Long Evans, and Lister Hooded) underwent comparative analysis of electrophysiological (auditory brainstem responses, ABRs) and behavioral measures after noise trauma induction to differentiate between strain-dependent trauma effects and more consistent changes across strains, such as frequency dependence or systematic temporal changes. Several hearing- and trauma-related characteristics were clearly strain-dependent. Lister Hooded rats had especially high hearing thresholds and were unable to detect a silent gap in continuous background noise but displayed the highest startle amplitudes. After noise exposure, ABR thresholds revealed a strain-dependent pattern of recovery. ABR waveforms varied in detail among rat strains, and the difference was most prominent at later peaks arising approximately 3.7 ms after stimulus onset. However, changes in ABR waveforms after trauma were small compared to consistent strain-dependent differences between individual waveform components. At the behavioral level, startle-based gap-prepulse inhibition (gap-PPI) was used to evaluate the occurrence and characteristics of tinnitus after noise exposure. A loss of gap-PPI was found in 33% of Wistar, 50% of Sprague Dawley, and 75% of Long Evans rats. Across strains, the most consistent characteristic was a frequency-specific pattern of the loss of gap-PPI, with the highest rates at approximately one octave above trauma. An additional range exhibiting loss of gap-PPI directly below trauma frequency was revealed in Sprague Dawley and Long Evans rats. Further research should focus on these frequency ranges when investigating the underlying mechanisms of tinnitus induction.

PMA treatment fosters rat retinal ganglion cell survival via TNF signaling

An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the cell to activate protective intracellular signals, including inflammatory cytokines. Our previous work showed that the treatment of Lister Hooded rat retinal cell cultures with 50 ng/mL phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, increases the survival of retinal ganglion cells (RGCs) kept in culture for 48 h after axotomy. Here we aim to analyze how PMA modulates the levels of TNF-α and IL-1β (both key inflammatory mediators) and the impact of this modulation on RGCs survival. We hypothesize that the increase in RGCs survival mediated by PMA treatment depends upon modulation of the levels of IL-1β and TNF-α. The effect of PMA treatment was assayed on cell viability, caspase 3 activation, TNF-α and IL-1β release and TNF receptor type I (TNFRI) and TNF receptor type II (TNFRII) levels. PMA treatment increases IL-1β and TNF-α levels in 15 min in culture and increases the release of both cytokines after 30 min and 24 h, respectively. Both IL-1β and TNF-α levels decrease after 48 h of PMA treatment. PMA treatment also induces an increase in TNFRII levels while decreasing TNFRI after 24 h. PMA also inhibited caspase-3 activation, and decreased ROS production and EthD-1/calcein ratio in retinal cell cultures leading to an increase in cell viability. The neutralization of IL-1β (anti-IL1β 0,1ng/mL), the neutralization of TNF-α (anti-TNF-α 0,1ng/mL) and the TNF-α inhibition using a recombinant soluble TNFRII abolished PMA effect on RGCs survival. These data suggest that PMA treatment induces IL1β and TNF-α release and modulation of TNFRI/TNFRII expression promoting RGCs survival after axotomy.

Strain comparisons in inhibitory discrimination learning and novel object recognition procedures

Strain differences in visual abilities and exploratory tendencies can confound rats’ performance in cognitive tests of learning and memory. In the present study we compared the performance of albino Wistar and pigmented Lister Hooded rats in appetitive conditioning and recognition memory procedures, specifically within-subjects inhibitory learning (A+ /AX-) and novel object recognition (NOR) variants. The inhibition task included an excitatory training stage and summation and retardation tests. Difference scores were used to help control for individual variation in baseline nosepoke responding. NOR was tested after a 10 min delay, following 24hr delay and using a recency variant. Discrimination ratios were used to control for individual variation in exploratory activity. In the inhibitory learning procedure, Lister Hooded showed more magazine activity prior to stimulus presentations than Wistar rats but this was a transient effect restricted to day 1 of excitatory training. There was no strain difference in associative learning at the excitatory training stage. The Wistars went on to show some performance advantage at the inhibitory discrimination stage and marginally stronger retardation test performance. In the NOR tasks, there was no significant effect of strain on cognitive performance, but the Wistars showed some advantage in the 10 min delay variant, whereas in the 24hr delay and relative recency NOR variants, the Lister Hooded rats showed some advantage. Overall the results of the present study confirm the suitability of Wistar rats for use in associative learning and basic NOR procedures.

Intensive longitudinal characterization of multidimensional biobehavioral dynamics in laboratory rats.

Rats have been used as animal models for human diseases for more than a century, yet a systematic understanding of basal biobehavioral phenotypes of laboratory rats is still missing. In this study, we utilize wireless tracking technology and videography, collect and analyze more than 130 billion data points to fill this gap, and characterize the evolution of behavior and physiology of group-housed male and female rats (n= 114) of the most commonly used strains (Lister Hooded, Long-Evans, Sprague-Dawley, and Wistar) throughout their development. The resulting intensive longitudinal data suggest the existence of strain and sex differences and bi-stable developmental states. Under standard laboratory 12-h light/12-h dark conditions, our study found the presence of multiple oscillations such as circatidal-like rhythms in locomotor activity. The overall findings further suggest that frequent movement along cage walls or thigmotaxic activity may be a physical feature of motion in constrained spaces, critically affecting the interpretation of basal behavior of rats in cages.

Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma

ABSTRACT Purpose A major challenge in glaucoma research is the lack of reproducible animal models of RGC and optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber. Methods Magnetic microsphere suspensions (20 µl of 5–20 mg/ml) were injected into the anterior chamber of BN (n = 9) or LH (N = 15) rats. Animals from each strain were divided into three groups, each receiving a different dose of microspheres. IOP was measured over 4 weeks using a rebound tonometer. Retinal ganglion cell (RGC) damage and function were assessed using scotopic electroretinograms (ERGs), retinal flatmounts and optic nerve histology. ANOVA and Student’s t-tests were used to analyse the data. Results A significant elevation in IOP was observed in BN rats receiving injections of 20 mg (37.18 ± 12.28 mmHg) or 10 mg microspheres/ml (36.95 ± 13.63 mmHg) when compared with controls (19.63 ± 4.29 mmHg) (p < .001) over 2 weeks. This correlated with a significant impairment of RGC function, as determined by scotopic ERG (p < .001), reduction in axon number (p < .05) and lower RGC density (P < .05) in animals receiving 20 mg or 10 mg microspheres/ml as compared with controls. LH rats receiving similar microsphere doses showed reduced scotopic ERG function (p < .001) after 2 weeks. No changes in IOP was seen in this strain, although a reduction in axon density was observed in optic nerve cross-sections (p < .05). Initial changes in IOP and ERG responses observed in BN rats remained unchanged for a duration of 7 weeks. In LH animals, ERG responses were decreased at 1–2 weeks and returned to control levels after 5 weeks. Conclusions Although this model was easily reproducible in BN rats, the phenotype of injury observed in LH rats was very different from that observed in BN animals. We suggest that differences in the glaucomatous response observed in these two strains may be ascribed to anatomical and physiological differences and merits further investigation.

Translational Difficulties in Querying Rats on “Orientation”

The aim of this study was to translate the “orientation” query of the ADAS-Cog inventory to rats and to investigate whether they can determine which time of the day they are. For this purpose, we established a modified Morris water-maze navigation task where the escape platform was placed onto various locations at different times of the day: “morning”, “noon” and “evening”. In each of these sessions rats swam a “query” trial and a “confirmatory” trial, 30 min apart. Lister Hooded rats randomly chose among the three possible target locations, while Long Evans rats partly followed a win-stay strategy by preferring to visit first to the platform position of the previous session. Despite simplifying the task to a morning–evening discrimination, Lister Hooded rats continued searching by chance, while Long Evans rats switched to the mentally less demanding random strategy. We then inserted a board into the pool which required longer swimming path from the animals when they were correcting an initial wrong choice, but this modification did not result in a change in the above strategies. Lastly, in a separate group of Long–Evans rats, the training conditions were modified inasmuch an incorrect choice was definitely punished by impeding the animals to correct it and confining them to a platform-free part of the maze for the whole trial period. However, even these stricter conditions were not sufficient to make the rats distinguish times of the day. The observed lack of time discrimination may source from an evolutionary built in mechanism characteristic for the rat species or this ability may have only been lost in laboratory rats.

Following of aging process in a new motor skill learning model, \u201cpot jumping\u201d in rats

Impairment of procedural memory is a frequent and severe symptom in many neurological and psychiatric diseases as well as during aging. Our aim was to establish an assay in rats in which procedural learning and changes in performance can be studied on the long term. The work was done in the frame of a larger project aiming to establish a complex cognitive animal test battery of high translational value. The equipment was a 190-cm-diameter circular water tank where 12 flower pots were placed upside down in a circle with increasing distances (18–46 cm) between the adjacent ones. Male Lister Hooded and Long-Evans rats were allowed to move on the pots for 3 min. The arena was filled with shallow water to make the rats stay on the pots. Animals were obviously motivated to move around on the pots; however, the distance which required jumping (> 26 cm) meant a barrier for some of them. Development of motor skill was measured by the longest distance successfully spanned. A relatively flat bell-shaped age dependence was observed, with a peak at 13 months of age. A gradual decline in performance could be observed after the age of 20 months which preceded the appearance of overt physical weakness. Long-Evans rats showed more homogeneous performance and higher individual stability than Lister Hooded rats. The method is appropriate to study the development of motor learning and to follow its age-dependent changes. It may also serve as an assay for testing potential drugs for improving motor skills and/or procedural memory.

Evolution of a maternal immune activation (mIA) model in rats: Early developmental effects

Maternal immune activation (mIA) in rodents is rapidly emerging as a key model for neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain limitations of current work in this field. Specifically, the lack of clear evidence for methodology chosen, identification of successful induction of mIA in the dams and investigation of male offspring only. We focus on gestational and early juvenile changes in offspring following mIA, as detailed information on these critical early developmental time points is sparse.Following strain (Wistar, Lister Hooded, Sprague Dawley) comparison and selection, and polyriboinosinic-polyribocytidylic acid (poly I:C) dose selection (2.5–15 mg/kg single or once daily for 5 days), mIA was induced in pregnant Wistar rats with 10 mg/kg poly I:C i.p. on gestational day (GD) 15. Early morphometric analysis was conducted in male and female offspring at GD21 and postnatal day (PD) 21, eight dams for each treatment at each time point were used, 32 in total. Subsequent microglia analysis was conducted at PD21 in a small group of offspring.Poly I:C at 10 mg/kg i.p. induced a robust, but variable, plasma IL-6 response 3 h post-injection and reduced body weight at 6 h and 24 h post-injection in two separate cohorts of Wistar rats at GD15. Plasma IL-6 was not elevated at PD21 in offspring or dams. Poly I:C-induced mIA did not affect litter numbers, but resulted in PD21 pup, and GD21 placenta growth restriction. Poly I:C significantly increased microglial activation at PD21 in male hippocampi.We have identified 10 mg/kg poly I:C i.p on GD15 as a robust experimental approach for inducing mIA in Wistar rats and used this to identify early neurodevelopmental changes. This work provides a framework to study the developmental trajectory of disease-relevant, sex-specific phenotypic changes in rats.

Chronic amphetamine treatment affects collicular-dependent behaviour

Distractibility can be defined as an attention deficit where orientation toward irrelevant targets cannot be inhibited. There is now mounting evidence that the superior colliculus is a key neural correlate of distractibility, with increased collicular-activity resulting in heightened distractibility. Heightened distractibility is reduced by amphetamine, which acutely suppresses collicular responsiveness. However, when amphetamine is used to treat distractibility, it is given chronically, yet no data exist on whether chronic amphetamine treatment affects the colliculus. Here, the effect of chronic amphetamine treatment was assessed in healthy hooded lister rats on two collicular dependent behaviours following a twenty-eight day treatment period: i) orienting to visual stimuli, and ii) height-dependent modulation of air-righting. We found no significant impact of amphetamine treatment on visual orienting despite showing dose-dependent decreases in orienting to repeated stimuli. However, we did find that treatment with amphetamine significantly reduced the ability to modulate righting according to the height the animal is dropped from – a function known to be dependent on the colliculus. We suggest that the results are in line with previous research showing acute amphetamine suppresses collicular activity and we speculate that the psychostimulant may increase receptive field size, altering time-to-impact calculations carried out by the colliculus during air-righting.

Validation of Drug Discrimination in the Lister Hooded Rat: Anti-Depressants

Validation of Drug Discrimination in the Lister Hooded Rat: Anti-Depressants

Self Administration of Ketamine in the Male Lister Hooded Rat: Data Considerations

Self Administration of Ketamine in the Male Lister Hooded Rat: Data Considerations

Further validation of the affective bias test for predicting antidepressant and pro-depressant risk: effects of pharmacological and social manipulations in male and female rats

RationaleAffective biases are hypothesised to contribute to the cause and treatment of mood disorders. We have previously found that affective biases, associated with learning and memory, are observed following acute treatments with a range of antidepressant and pro-depressant manipulations.ObjectiveThis study aimed to test if similar biases are observed in male and female Sprague Dawley (SD) rats. We also test whether the stress hormone, corticosterone, induces a negative bias in the affective bias test (ABT) consistent with its putative role in the development of depression. We then use a meta-analysis to compare our findings with data published for the Lister Hooded rats.MethodsThe ABT uses a within-subject study design where animals learn to associate distinct digging substrates, encountered on different days, with the same value food reward. Exposure to one substrate is paired with a treatment manipulation (drug or environmental) and the other with a control condition. A preference test is used to test if the treatment has induced a positive or negative bias.ResultsConsistent with previous data, both male and female SD rats exhibit similar positive affective biases following treatment with the antidepressant, venlafaxine, and social play and negative affective biases following FG 7142 (benzodiazepine inverse agonist) and social stress. Acute treatment with corticosterone induced a negative bias.ConclusionsThese data add to the translational validity of the ABT and suggest that corticosterone can induce a negative affective bias following acute treatment, an effect which may contribute to its long-term effects on mood.

A general protocol of ultra-high resolution MR angiography to image the cerebro-vasculature in 6 different rats strains at high field

BackgroundDifferences in the cerebro-vasculature among strains as well as individual animals might explain variability in animal models and thus, a non-invasive method tailored to image cerebral vessel of interest with high signal to noise ratio is required. New methodExperimentally, we describe a new general protocol of three-dimensional time-of-flight magnetic resonance angiography to visualize non-invasively the cerebral vasculature in 6 different rat strains. Flow compensated angiograms of Sprague Dawley, Wistar Kyoto, Lister Hooded, Long Evans, Fisher 344 and Spontaneous Hypertensive Rat strains were obtained without the use of contrast agents. At 11.7T using a repetition time of 60ms, an isotropic resolution of up to 62μm was achieved; total imaging time was 98min for a 3D data set. ResultsThe visualization of the cerebral arteries was improved by removing extra-cranial vessels prior to the calculation of maximum intensity projection to obtain the angiograms. Ultimately, we demonstrate that the newly implemented method is also suitable to obtain angiograms following middle cerebral artery occlusion, despite the presence of intense vasogenic edema 24h after reperfusion. Comparison with existing methodsThe careful selection of the excitation profile and repetition time at a higher static magnetic field allowed an increase in spatial resolution to reliably detect of the hypothalamic artery, the anterior choroidal artery as well as arterial branches of the peri-amygdoidal complex and the optical nerve in six different rat strains. ConclusionsMR angiography without contrast agent can be utilized to study cerebro-vascular abnormalities in various animal models.

Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing Antibody

ABSTRACTPurpose: To detect the safety of intravitreal injection of anti-connective tissue growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing antibody for experimental animal studies.Methods: Forty-five Lister Hooded male pigmented rats were divided into five groups that received IVAC (2 μl) corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 μg/ml (E), equal to 1.25, 2.5, 6.25, and 12.5 µg/ml of antibody concentration in rat vitreous, respectively. The sham group (A) received 2 μl of normal saline. Full field electroretinography (ERG) was performed at baseline and on days 7 and 28 after IVAC. The animals were euthanized and the corresponding eyes were subjected to routine histopathology, immunohistochemistry for glial fibrillary acidic protein (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay.Results: Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89 ± 71.2 and 178.57 ± 55.58 μV, respectively, at baseline which significantly reduced to 79.31 ± 52.59 and 128.73 ± 41.61 μV, respectively, after 28 days in group E (p < 0.05). There was no significant reduction of amplitudes in other groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were significantly decreased in group E as compared to other groups. GFAP immune reactivity was not significant in any of the groups. TUNEL test showed inner retinal neural cell apoptosis only in group E.Conclusions: ERG, histopathologic, and apoptotic assays revealed no toxic effects of 10–50 μg/ml of IVAC in rat eyes. Using 100 μg/ml IVAC led to a significant toxic effect in terms of functional, histopathologic, and TUNEL findings.

Place cells on a maze encode routes rather than destinations.

Hippocampal place cells fire at different rates when a rodent runs through a given location on its way to different destinations. However, it is unclear whether such firing represents the animal's intended destination or the execution of a specific trajectory. To distinguish between these possibilities, Lister Hooded rats (n = 8) were trained to navigate from a start box to three goal locations via four partially overlapping routes. Two of these led to the same goal location. Of the cells that fired on these two routes, 95.8% showed route-dependent firing (firing on only one route), whereas only two cells (4.2%) showed goal-dependent firing (firing similarly on both routes). In addition, route-dependent place cells over-represented the less discriminable routes, and place cells in general over-represented the start location. These results indicate that place cell firing on overlapping routes reflects the animal's route, not its goals, and that this firing may aid spatial discrimination.

Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development

Objective: The development of retinotectal pathways form precise topographical maps is usually completed by the third postnatal week. Cytokines participate in the development and plasticity of the nervous system. We have previously shown that in vivo treatment with interleukin 2 disrupts the retinocollicular topographical order in early stages of development. Therefore, we decided to study the effect of a single intravitreous injection of IL-6 upon retinotectal circuitry in neonates and juvenile rats. Materials and Methods: Lister Hooded rats received an intravitreous injection of IL-6 (50 ng/ml) or vehicle (PBS) at either postnatal day (PND)10 or PND30 and the ipsilateral retinotectal pathway was evaluated 4 or 8 days later, respectively. Results: Our data showed that, at different stages of development, a single IL-6 intravitreous treatment did not produce an inflammatory response and increased retinal axon innervation throughout the visual layers of the superior colliculus. Conclusions: Taken together, our data provide the first evidence that a single intravitreous injection with IL-6 leads to sprouting in the subcortical visual connections and suggest that small changes in IL-6 levels might be sufficient to impair the correct neuronal circuitry fine-tuning during brain development.