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We develop a method for selecting meaningful learning strategies based solely on the behavioral data of a single individual in a learning experiment. We use simple Activity-Credit Assignment algorithms to model the different strategies and couple them with a novel hold-out statistical selection method. Application on rat behavioral data in a continuous T-maze task reveals a particular learning strategy that consists in chunking the paths used by the animal. Neuronal data collected in the dorsomedial striatum confirm this strategy.
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Aprendizaje , Memoria , Ratas , Animales , Aprendizaje/fisiología , Cuerpo Estriado/fisiología , Toma de Decisiones/fisiología , CogniciónRESUMEN
Unilateral vestibular loss (UVL) induces a characteristic vestibular syndrome composed of various posturo-locomotor, oculomotor, vegetative and perceptivo-cognitive symptoms. Functional deficits are progressively recovered over time during vestibular compensation, that is supported by the expression of multiscale plasticity mechanisms. While the dynamic of post-UVL posturo-locomotor and oculomotor deficits is well characterized, the expression over time of the cognitive deficits, and in particular spatial memory deficits, is still debated. In this study we aimed at investigating spatial memory deficits and their recovery in a rat model of unilateral vestibular neurectomy (UVN), using a wide spectrum of behavioral tasks. In parallel, we analyzed markers of hippocampal plasticity involved in learning and memory. Our results indicate the UVN affects all domains of spatial memory, from working memory to reference memory and object-in-place recognition. These deficits are associated with long-lasting impaired plasticity in the ipsilesional hippocampus. These results highlight the crucial role of symmetrical vestibular information in spatial memory and contribute to a better understanding of the cognitive disorders observed in vestibular patients.
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Enfermedades Vestibulares , Vestíbulo del Laberinto , Ratas , Animales , Memoria Espacial , Vestíbulo del Laberinto/metabolismo , Hipocampo/metabolismo , Trastornos de la MemoriaRESUMEN
BACKGROUND: Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss. METHODS: We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron's membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions' recovery were assessed with appropriate qualitative and quantitative evaluations. RESULTS: We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome's intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment. CONCLUSIONS: We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients.
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Antiinflamatorios/uso terapéutico , Metilprednisolona/uso terapéutico , Plasticidad Neuronal/efectos de los fármacos , Recuperación de la Función/efectos de los fármacos , Neuronitis Vestibular/tratamiento farmacológico , Núcleos Vestibulares/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Metilprednisolona/farmacología , Actividad Motora/efectos de los fármacos , Plasticidad Neuronal/fisiología , Equilibrio Postural/efectos de los fármacos , Ratas , Ratas Long-Evans , Recuperación de la Función/fisiología , Neuronitis Vestibular/fisiopatología , Núcleos Vestibulares/fisiopatologíaRESUMEN
The medial (MEC) and the lateral (LEC) regions of the entorhinal cortex send a major input to the hippocampus and have been proposed to play a foremost role in combining spatial and non-spatial attributes of episodic memory. In addition, it has been recently suggested that the MEC is involved in the processing of information in a global reference frame and the LEC in the processing of information in a local reference frame. Whether these putative functions could be generalized to navigation contexts has not been established yet. To address this hypothesis, rats with MEC or LEC NMDA-induced lesions were trained in two versions of a navigation task in the water maze, a global cue condition in which they had to use distal room cues and a local cue condition in which they had to use 3 objects placed in the pool. In the global cue condition, MEC-lesioned rats exhibited slower acquisition and were not able to precisely locate the submerged platform during the probe trial. In contrast LEC-lesioned rats exhibited control-like performance. In the local cue condition, navigational abilities were spared in both lesion groups. In addition when the 3 different objects were replaced by 3 identical objects, all groups maintained their navigation accuracy suggesting that the identity of objects is not crucial for place navigation. Overall, the results indicate that the MEC is necessary for place navigation using a global reference frame. In contrast, navigation using a local reference frame does not require the LEC nor the MEC.
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Conducta Animal/fisiología , Corteza Entorrinal/fisiopatología , Aprendizaje por Laberinto/fisiología , Navegación Espacial/fisiología , Animales , Corteza Entorrinal/patología , Masculino , Ratas , Ratas Long-EvansRESUMEN
The entorhinal-hippocampus network plays a central role in navigation and episodic memory formation. To investigate these interactions, we examined the effect of medial entorhinal cortex lesions on hippocampal place cell activity. Since the medial entorhinal cortex is suggested to play a role in the processing of self-motion information, we hypothesised that such processing would be necessary for maintaining stable place fields in the absence of environmental cues. Place cells were recorded as medial entorhinal cortex-lesioned rats explored a circular arena during five 16-min sessions comprising a baseline session with all sensory inputs available followed by four sessions during which environmental (i.e. visual, olfactory, tactile) cues were progressively reduced to the point that animals could rely exclusively on self-motion cues to maintain stable place fields. We found that place field stability and a number of place cell firing properties were affected by medial entorhinal cortex lesions in the baseline session. When rats were forced to rely exclusively on self-motion cues, within-session place field stability was dramatically decreased in medial entorhinal cortex rats relative to SHAM rats. These results support a major role of the medial entorhinal cortex in processing self-motion cues, with this information being conveyed to the hippocampus to help anchor and maintain a stable spatial representation during movement.
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Place recognition is a complex process involving idiothetic and allothetic information. In mammals, evidence suggests that visual information stemming from the temporal and parietal cortical areas ('what' and 'where' information) is merged at the level of the entorhinal cortex (EC) to build a compact code of a place. Local views extracted from specific feature points can provide information important for view cells (in primates) and place cells (in rodents) even when the environment changes dramatically. Robotics experiments using conjunctive cells merging 'what' and 'where' information related to different local views show their important role for obtaining place cells with strong generalization capabilities. This convergence of information may also explain the formation of grid cells in the medial EC if we suppose that: (1) path integration information is computed outside the EC, (2) this information is compressed at the level of the EC owing to projection (which follows a modulo principle) of cortical activities associated with discretized vector fields representing angles and/or path integration, and (3) conjunctive cells merge the projections of different modalities to build grid cell activities. Applying modulo projection to visual information allows an interesting compression of information and could explain more recent results on grid cells related to visual exploration. In conclusion, the EC could be dedicated to the build-up of a robust yet compact code of cortical activity whereas the hippocampus proper recognizes these complex codes and learns to predict the transition from one state to another.
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Corteza Entorrinal/fisiología , Primates/fisiología , Robótica , Roedores/fisiología , Animales , Modelos NeurológicosRESUMEN
Entorhinal grid cells are thought to provide a 2D spatial metric of the environment. In this study we demonstrate that in a familiar 1D circular track (i.e., a continuous space) grid cells display a novel 1D equidistant firing pattern based on integrated distance rather than travelled distance or time. In addition, field spacing is increased compared to a 2D open field, probably due to a reduced access to the visual cue in the track. This metrical modification is accompanied by a change in LFP theta oscillations, but no change in intrinsic grid cell rhythmicity, or firing activity of entorhinal speed and head-direction cells. These results suggest that in a 1D circular space grid cell spatial selectivity is shaped by path integration processes, while grid scale relies on external information.
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Subcortical band heterotopia (SBH), also known as doublecortex syndrome, is a malformation of cortical development resulting from mutations in the doublecortin gene (DCX). It is characterized by a lack of migration of cortical neurons that accumulate in the white matter forming a heterotopic band. Patients with SBH may present mild to moderate intellectual disability as well as epilepsy. The SBH condition can be modeled in rats by in utero knockdown (KD) of Dcx. The affected cells form an SBH reminiscent of that observed in human patients and the animals develop a chronic epileptic condition in adulthood. Here, we investigated if the presence of a SBH is sufficient to induce cognitive impairment in juvenile Dcx-KD rats, before the onset of epilepsy. Using a wide range of behavioral tests, we found that the presence of SBH did not appear to affect motor control or somatosensory processing. In addition, cognitive abilities such as learning, short-term and long-term memory, were normal in pre-epileptic Dcx-KD rats. We suggest that the SBH presence is not sufficient to impair these behavioral functions.
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Conducta Animal , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/psicología , Cognición , Modelos Animales de Enfermedad , Epilepsia/genética , Discapacidad Intelectual/genética , Animales , Ansiedad/genética , Enfermedades Asintomáticas , Movimiento Celular , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/complicaciones , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/embriología , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/genética , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Electroporación , Conducta Exploratoria , Sustancia Gris/anomalías , Sustancia Gris/embriología , Aprendizaje , Aprendizaje por Laberinto , Memoria , Proteínas Asociadas a Microtúbulos/deficiencia , Proteínas Asociadas a Microtúbulos/genética , Mosaicismo , Neuropéptidos/deficiencia , Neuropéptidos/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/toxicidad , Ratas , Prueba de Desempeño de Rotación con Aceleración Constante , Sensación , Sustancia Blanca/anomalías , Sustancia Blanca/embriologíaRESUMEN
It is now widely accepted that the entorhinal cortex (EC) plays a pivotal role in the processing of spatial information and episodic memory. The EC is segregated into two sub-regions, the medial EC (MEC) and the lateral EC (LEC) but a comprehensive understanding of their roles across multiple behavioral contexts remains unclear. Considering that it is still useful to investigate the impact of lesions of EC on behavior, we review the contribution of lesion approach to our knowledge of EC functions. We show that the MEC and LEC play different roles in the processing of spatial and non-spatial information. The MEC is necessary to the use of distal but not proximal landmarks during navigation and is crucial for path integration, in particular integration of linear movements. Consistent with predominant hypothesis, the LEC is important for combining the spatial and non-spatial aspects of the environment. However, object exploration studies suggest that the functional segregation between the MEC and the LEC is not as clearly delineated and is dependent on environmental and behavioral factors. Manipulation of environmental complexity and therefore of cognitive demand shows that the MEC and the LEC are not strictly necessary to the processing of spatial and non-spatial information. In addition we suggest that the involvement of these sub-regions can depend on the kind of behavior, i.e., navigation or exploration, exhibited by the animals. Thus, the MEC and the LEC work in a flexible manner to integrate the "what" and "where" information in episodic memory upstream the hippocampus.
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Path integration is a navigation strategy that requires animals to integrate self-movements during exploration to determine their position in space. The medial entorhinal cortex (MEC) has been suggested to play a pivotal role in this process. Grid cells, head-direction cells, border cells as well as speed cells within the MEC collectively provide a dynamic representation of the animal position in space based on the integration of self-movements. All these cells are strongly modulated by theta oscillations, thus suggesting that theta rhythmicity in the MEC may be essential for integrating and coordinating self-movement information during navigation. In this study, we first show that excitotoxic MEC lesions, but not dorsal hippocampal lesions, impair the ability of rats to estimate linear distances based on self-movement information. Next, we report similar deficits following medial septum inactivation, which strongly impairs theta oscillations in the entorhinal-hippocampal circuits. Taken together, these findings demonstrate a major role of the MEC and MS in estimating distances to be traveled, and point to theta oscillations within the MEC as a neural mechanism responsible for the integration of information generated by linear self-displacements.
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Conducta Animal , Corteza Entorrinal/fisiopatología , Hipotálamo/fisiopatología , Locomoción , Percepción Espacial , Navegación Espacial , Procesamiento Espacial , Ritmo Teta , Animales , Conducta Animal/efectos de los fármacos , Corteza Entorrinal/efectos de los fármacos , Corteza Entorrinal/patología , Agonistas de Aminoácidos Excitadores/toxicidad , Agonistas de Receptores de GABA-A/toxicidad , Hipotálamo/efectos de los fármacos , Hipotálamo/patología , Ácido Iboténico/toxicidad , Locomoción/efectos de los fármacos , Masculino , N-Metilaspartato/toxicidad , Ratas Long-Evans , Percepción Espacial/efectos de los fármacos , Navegación Espacial/efectos de los fármacos , Procesamiento Espacial/efectos de los fármacos , Ritmo Teta/efectos de los fármacosRESUMEN
The entorhinal-hippocampal circuitry has been suggested to play an important role in episodic memory but the contribution of the entorhinal cortex remains elusive. Predominant theories propose that the medial entorhinal cortex (MEC) processes spatial information whereas the lateral entorhinal cortex (LEC) processes non spatial information. A recent study using an object exploration task has suggested that the involvement of the MEC and LEC spatial and non-spatial information processing could be modulated by the amount of information to be processed, i.e. environmental complexity. To address this hypothesis we used an object exploration task in which rats with excitotoxic lesions of the MEC and LEC had to detect spatial and non-spatial novelty among a set of objects and we varied environmental complexity by decreasing the number of objects or amount of object diversity. Reducing diversity resulted in restored ability to process spatial and non-spatial information in MEC and LEC groups, respectively. Reducing the number of objects yielded restored ability to process non-spatial information in the LEC group but not the ability to process spatial information in the MEC group. The findings indicate that the MEC and LEC are not strictly necessary for spatial and non-spatial processing but that their involvement depends on the complexity of the information to be processed.
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Corteza Entorrinal/fisiología , Ambiente , Conducta Exploratoria/fisiología , Conducta Espacial/fisiología , Animales , Corteza Entorrinal/lesiones , Hipocampo/lesiones , Hipocampo/fisiología , Locomoción/fisiología , Masculino , Vías Nerviosas/fisiología , Ratas , Ratas Long-Evans , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The increasing use of mice models in cognitive tasks that were originally designed for rats raises crucial questions about cross-species comparison in the study of spatial cognition. The present review focuses on the major neuroethological differences existing between mice and rats, with particular attention given to the neurophysiological basis of space coding. While little difference is found in the basic properties of space representation in these two species, it appears that the stability of this representation changes more drastically over time in mice than in rats. We consider several hypotheses dealing with attentional, perceptual, and genetic aspects and offer some directions for future research that might help in deciphering hippocampal function in learning and memory processes. WIREs Cogn Sci 2016, 7:406-421. doi: 10.1002/wcs.1411 For further resources related to this article, please visit the WIREs website.
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Encéfalo/fisiología , Cognición/fisiología , Percepción Espacial/fisiología , Procesamiento Espacial/fisiología , Animales , Atención/fisiología , Conducta Animal , Señales (Psicología) , Hipocampo/fisiología , Ratones , Células de Lugar/fisiología , Ratas , Aprendizaje Espacial/fisiología , Navegación Espacial/fisiología , Especificidad de la EspecieRESUMEN
Since the discovery of place cells, the hippocampus is thought to be the neural substrate of a cognitive map. The later discovery of head direction cells, grid cells and border cells, as well as of cells with more complex spatial signals, has led to the idea that there is a brain system devoted to providing the animal with the information required to achieve efficient navigation. Current questioning is focused on how these signals are integrated in the brain. In this review, we focus on the issue of how self-localization is performed in the hippocampal place cell map. To do so, we first shortly review the sensory information used by place cells and then explain how this sensory information can lead to two coding modes, respectively based on external landmarks (allothetic information) and self-motion cues (idiothetic information). We hypothesize that these two modes can be used concomitantly with the rat shifting from one mode to the other during its spatial displacements. We then speculate that sequential reactivation of place cells could participate in the resetting of self-localization under specific circumstances and in learning a new environment. Finally, we provide some predictions aimed at testing specific aspects of the proposed ideas.
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Navigation in rodents depends on both self-motion (idiothetic) and external (allothetic) information. Idiothetic information has a predominant role when allothetic information is absent or irrelevant. The vestibular system is a major source of idiothetic information in mammals. By integrating the signals generated by angular and linear accelerations during exploration, a rat is able to generate and update a vector pointing to its starting place and to perform accurate return. This navigation strategy, called path integration, has been shown to involve a network of brain structures. Among these structures, the entorhinal cortex (EC) may play a pivotal role as suggested by lesion and electrophysiological data. In particular, it has been recently discovered that some neurons in the medial EC display multiple firing fields producing a regular grid-like pattern across the environment. Such regular activity may arise from the integration of idiothetic information. This hypothesis would be strongly strengthened if it was shown that manipulation of vestibular information interferes with grid cell activity. In the present paper we review neuroanatomical and functional evidence indicating that the vestibular system influences the activity of the brain network involved in spatial navigation. We also provide new data on the effects of reversible inactivation of the peripheral vestibular system on the EC theta rhythm. The main result is that tetrodotoxin (TTX) administration abolishes velocity-controlled theta oscillations in the EC, indicating that vestibular information is necessary for EC activity. Since recent data demonstrate that disruption of theta rhythm in the medial EC induces a disorganization of grid cell firing, our findings indicate that the integration of idiothetic information in the EC is essential to form a spatial representation of the environment.
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Recent interest in the neural bases of spatial navigation stems from the discovery of neuronal populations with strong, specific spatial signals. The regular firing field arrays of medial entorhinal grid cells suggest that they may provide place cells with distance information extracted from the animal's self-motion, a notion we critically review by citing new contrary evidence. Next, we question the idea that grid cells provide a rigid distance metric. We also discuss evidence that normal navigation is possible using only landmarks, without self-motion signals. We then propose a model that supposes that information flow in the navigational system changes between light and dark conditions. We assume that the true map-like representation is hippocampal and argue that grid cells have a crucial navigational role only in the dark. In this view, their activity in the light is predominantly shaped by landmarks rather than self-motion information, and so follows place cell activity; in the dark, their activity is determined by self-motion cues and controls place cell activity. A corollary is that place cell activity in the light depends on non-grid cells in ventral medial entorhinal cortex. We conclude that analysing navigational system changes between landmark and no-landmark conditions will reveal key functional properties.
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Corteza Entorrinal/fisiología , Hipocampo/fisiología , Modelos Neurológicos , Células Piramidales/fisiología , Conducta Espacial/fisiología , Potenciales de Acción/fisiología , Animales , Corteza Entorrinal/citología , Hipocampo/citología , Vías Nerviosas/fisiología , RatasRESUMEN
It is known that the entorhinal cortex plays a crucial role in spatial cognition in rodents. Neuroanatomical and electrophysiological data suggest that there is a functional distinction between 2 subregions within the entorhinal cortex, the medial entorhinal cortex (MEC), and the lateral entorhinal cortex (LEC). Rats with MEC or LEC lesions were trained in 2 navigation tasks requiring allothetic (water maze task) or idiothetic (path integration) information processing and 2-object exploration tasks allowing testing of spatial and nonspatial processing of intramaze objects. MEC lesions mildly affected place navigation in the water maze and produced a path integration deficit. They also altered the processing of spatial information in both exploration tasks while sparing the processing of nonspatial information. LEC lesions did not affect navigation abilities in both the water maze and the path integration tasks. They altered spatial and nonspatial processing in the object exploration task but not in the one-trial recognition task. Overall, these results indicate that the MEC is important for spatial processing and path integration. The LEC has some influence on both spatial and nonspatial processes, suggesting that the 2 kinds of information interact at the level of the EC.
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Corteza Entorrinal/fisiología , Percepción Espacial/fisiología , Conducta Espacial/fisiología , Animales , Cognición/fisiología , Conducta Exploratoria/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Long-EvansRESUMEN
Although rats are able to build complex spatial representations of their surroundings during exploration, the nature of the encoded information is still a matter for debate. In particular, it is not well established if rats can process the topological structure of the environment in such a way that they are aware of the connections existing between remote places. Here, rats were first exposed for four 5-min trials to a complex environment divided into several sectors that were separated by doors allowing either unrestricted or restricted access to other sectors. In the fifth test trial, we measured the behavior of the animals while they explored the same environment in which, however, they faced changes that either altered or did not alter the topological structure of the environment. In experiment 1, closing previously opened doors prevented the rat from having direct access between corresponding sectors. In experiment 2, opening previously closed doors allowed direct access between sectors that had not been directly accessible. In each experiment, control doors allowed us to discard the mere influence of door manipulation. We compared the rats' exploratory behavior in response to door manipulations that either strongly altered or did not alter the ability to commute between sectors and found evidence that the animals displayed differential reactions to the two types of door manipulations. This implies that during exploration rats build a precise map of the connectivity of space that can be flexibly updated and used for efficient navigation.
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Conducta Exploratoria , Orientación , Ratas/psicología , Animales , Ambiente , Masculino , Actividad Motora , Ratas Long-Evans/psicología , Percepción EspacialRESUMEN
Considerable evidence has shown a clear dissociation between the dorsomedial (DMS) and the dorsolateral (DLS) striatum in instrumental conditioning. In particular, DMS activity is necessary to form action-outcome associations, whereas the DLS is required for developing habitual behavior. However, few studies have investigated whether a similar dissociation exists in more complex goal-directed learning processes. The present study examined the role of the two structures in such complex learning by analyzing the effects of excitotoxic DMS and DLS lesions during the acquisition and extinction of spatial alternation behavior, in a continuous alternation T-maze task. We demonstrate that DMS and DLS lesions have opposite effects, the former impairing and the latter improving animal performance during learning and extinction. DMS lesions may impair the acquisition of spatial alternation behavior by disrupting the signal necessary to link a goal with a specific spatial sequence. In contrast, DLS lesions may accelerate goal-driven strategies by minimizing the influence of external stimuli on the response, thus increasing the impact of action-reward contingencies. Taken together, these results suggest that DMS- and DLS-mediated learning strategies develop in parallel and compete for the control of the behavioral response early in learning.