Efectos de la edad y el sexo sobre la memoria espacial de ratas Wistar en el laberinto radial de 8 brazos

Trabajo de InvestigaciónEl presente estudio tuvo como objetivo evaluar el desempeño de 24 ratas Wistar en una tarea de memoria espacial, según las características de sexo y edad (ratas jóvenes y ratas adultas). Para este fin, se llevó a cabo una fase inicial de habituación de 10 minuto diarios en el laberinto radial de Olton, y una fase de entrenamiento de una tarea de memoria espacial durante 27 sesiones.INTRODUCCIÓN Y ASPECTOS GENERALES 1. RESUMEN 2. JUSTIFICACIÓN 3. MARCO TEÓRICO 4. MÉTODO 5. RESULTADOS 6. DISCUSIÓN Y CONCLUSIONES BIBLIOGRAFÍA ANEXOSPregradoPsicólog

Parameters.

<p>Parameter values used in Figs <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005702#pcbi.1005702.g002" target="_blank">2</a> and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005702#pcbi.1005702.g003" target="_blank">3</a> were listed.</p

Topographic mapping implemented by growth cone chemotaxis.

<p><b>(A)</b> The receptors were activated by guidance cue binding. Dose-response of receptor activation was plotted in right panel. <b>(B)</b> The chemotactic growth cone in (A) prefers a specific ligand concentration that is inversely proportional to the receptor expression level. <b>(C)</b> Linear topographic mapping was produced by an EphA gradient along the retinal nasal-temporal (NT) axis and an ephrinA gradient along the tectal rostral-caudal (RC) axis. Dashed arrows indicate corresponding receptor expression levels and preferred ligand concentrations. The applied gradients were and . <b>(D)</b> Two possible molecular mechanisms by which the guidance cue is transduced to an intracellular signal through the receptor. <b>(D(i))</b> Guidance cue-unbound receptors were active. <b>(D(ii))</b> Two kinds of receptors competitively bind the guidance cue so that these receptors effectively suppress each other. <b>(E)</b> The chemotactic growth cone in (D) prefers a specific ligand concentration that linearly increases with the receptor expression level. <b>(F)</b> Linear topographic mapping was produced by an EphB gradient along the retinal dorsal-ventral (DV) axis and an ephrinB gradient along the tectal medial-lateral (ML) axis. The applied gradients were and .</p

Two types of topographic maps in the retinotectal system.

<p><b>(A, B)</b> Topographic mapping from the retina to the tectum is encoded by orthogonal gradients of EphA and EphB receptors in the retina and of their ligands, ephrinA and ephrinB, in the tectum or SC. <b>(C, D)</b> The EphA/ephrinA- and EphB/ephrinB-encoded topographic mappings exhibit opposite receptor expression level-dependent ligand concentration preferences. These were categorized as types 1 and 2 in this study.</p

Mechanism of ligand concentration preferences by switching attraction and repulsion.

<p><b>(A)</b> Phase diagram depicting parameter regions of the four chemotactic response patterns. The dashed lines indicate critical lines corresponding to a ratio of <i>h</i>(<i>D</i>_<i>A</i>/<i>k</i>_<i>A</i>) to <i>h</i>(<i>D</i>_<i>I</i>/<i>k</i>_<i>I</i>). Because <i>h</i>(<i>D</i>/<i>k</i>) is a monotonically decreasing function of <i>D</i>/<i>k</i> (inset), the critical lines move with changes in <i>D</i>_<i>A</i>/<i>k</i>_<i>A</i> and <i>D</i>_<i>I</i>/<i>k</i>_<i>I</i>. <b>(B-E)</b> Various chemotactic responses (i.e., <i>ΔE</i>/<i>E</i>*) to guidance cue concentrations were derived: <b>(B)</b> bidirectional repulsion-to-attraction, <b>(C)</b> unidirectional repulsion, <b>(D)</b> unidirectional attraction and <b>(E)</b> bidirectional attraction-to-repulsion (BAR). Dashed arrows indicate the direction of concentration changes resulting from attractive or repulsive migration. In the BAR response, the x-intercept indicated by the black arrow corresponds to the preferred guidance cue concentration. The model parameters are listed in <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005702#pcbi.1005702.t001" target="_blank">Table 1</a></b>.</p

The model of the intracellular growth cone chemotactic process.

<p><b>(A)</b> A schematic of the one-dimensional model growth cone encountering an extracellular gradient of guidance cues. <b>(B)</b> The model growth cone’s components: a guidance cue (G) regulates an activator (A) and an inhibitor (I) of the effector (E). <b>(C, D)</b> Following exposure to a linear extracellular gradient of G (<i>G</i>(<i>x</i>) = <i>G</i>* + <i>gx</i>), gradients of A and I are formed across the growth cone, thereby forming a gradient of E. If the gradient of E orients to the extracellular gradient (<i>ΔE</i> > 0), then the growth cone shows attraction (C), but otherwise (<i>ΔE</i> < 0), it shows repulsion (D). The model parameters are listed in <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005702#pcbi.1005702.t001" target="_blank">Table 1</a></b>.</p

Shock procedure in the extended model.

<p><b>(A, B)</b> CS and US schedules; after extinction training of the partially reinforced fear memory, an additional CS-US pairing was applied, with the US being three times stronger <b>(A)</b> or the same intensity <b>(B)</b>. <b>(C, D)</b> The blue, green, red and black lines indicate the activities of the LA (persistent neurons), vmPFC (extinction neurons), ITC (another group of extinction neurons) and CEA (fear neurons), respectively. <b>(E, F)</b> The blue, green, red and black lines indicate the learning signals that changed the weights of CS-related synaptic input to the LA, vmPFC, ITC and CEA, respectively. Note that overlapped lines were changed to dashed lines to make them visible. <b>(G)</b> Final activity levels of the CEA (fear neural unit) after re-extinction training were plotted depending on the US intensity.</p

Fear memory in the extended model when the vmPFC was activated and silenced.

<p><b>(A)</b> Schedules of CS and US; the presentation schedules for the CS and US during fear conditioning and extinction were the same as those used in the basic model (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.g002" target="_blank">Fig 2A</a>), but the resting phase, during which neither the CS nor the US was presented, and the retrieval phase, during which only the CS was presented to evaluate extinction memory, were set after extinction. <b>(B-F)</b> Extended model simulation results for the control condition <b>(B)</b>, vmPFC activation during extinction <b>(C)</b>, vmPFC activation during retrieval <b>(D)</b>, vmPFC silencing during extinction <b>(E)</b> and vmPFC silencing during retrieval <b>(F)</b>. The blue, green, red and black lines indicate the activity of the LA (persistent neurons), vmPFC (extinction neurons), ITC (another group of extinction neurons) and CEA (fear neurons), respectively. Note that overlapping lines were changed to dashed lines to make them visible.</p

Partial reinforcement effect and the neural circuit models.

<p><b>(A, B)</b> During fear conditioning, a CS, <i>e</i>.<i>g</i>., a tone, was fully (in the full reinforcement schedule <b>(A)</b>) or partially (in the partial reinforcement schedule <b>(B)</b>) paired several times with a US, <i>e</i>.<i>g</i>., electric foot shock (<b>left panels</b>). The fear memory formed during fear conditioning can be diminished by extinction training, during which the CS is repeatedly presented alone, without the US (<b>right panels</b>). <b>(C)</b> Conditioned responses to the CS, which are usually measured as the degree of behavioral freezing responses, are depicted during fear conditioning and extinction. The fear memory (measured as the degree of behavioral freezing responses) that was acquired through the partial reinforcement schedule with P(US|CS)<1 exhibits a PREE (<b>blue line</b>), which is evident as increased resistance to extinction compared to that of the fear memory acquired through the full reinforcement schedule with P(US|CS) = 1 (<b>black line</b>). <b>(D, E)</b> The two neural circuit models are shown as schematics. Black and blue lines describe synaptic connections and the learning signals that regulate plasticity at synapses indicated by black open circles, respectively. <b>(D)</b> The basic model based on fear, persistent and extinction neural units (F, P and E). CS-related input activates all the units, and the extinction neural unit inhibits the fear neural unit, the activity of which represents the strength of the fear memory (black lines) (eqs (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e001" target="_blank">1</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e003" target="_blank">3</a>)). The efficacy of CS-related input to the fear, persistent and extinction neural units changes based on the learning signals (blue lines) (eqs (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e004" target="_blank">4</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e006" target="_blank">6</a>)). <b>(E)</b> Extended model including subregions of the amygdala (the LA, CEA and ITC) as well as the vmPFC. In this model, the LA and CEA correspond to persistent and fear neural units, respectively, and there are two extinction neural units: the ITC and vmPFC. CS-related input activates all subregions, and the ITC receives excitatory input from the vmPFC and inhibits the CEA (black lines) (eqs (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e007" target="_blank">7</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e010" target="_blank">10</a>)). A behavioral fear response was triggered by the CEA. The efficacy of plastic synapses (black open circles) changed based on learning signals (blue lines) (eqs (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e011" target="_blank">11</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.e014" target="_blank">14</a>)). Parameter values are listed in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005099#pcbi.1005099.s010" target="_blank">S1 Table</a>.</p

Fear memory acquired during the full and partial reinforcement schedules in the basic model.

<p>Basic model simulation results for the full and partial reinforcement schedules are presented in the left <b>(A, C, E and G)</b> and right <b>(B, D, F and H)</b> columns, respectively. <b>(A, B)</b> CS and US schedules during fear conditioning and extinction. <b>(C, D)</b> The black, blue and red lines indicate the activity of the fear, persistent and extinction neural units, respectively. <b>(E, F)</b> The black, blue and red lines indicate the synaptic weights of the CS-related inputs to the fear, persistent and extinction neural units, respectively. <b>(G, H)</b> The black, blue and red lines indicate the learning signals that changed the weights of CS-related synaptic inputs to the fear, persistent and extinction neural units, respectively. Note that overlapping lines were changed to dashed lines to make them visible. <b>(I-L)</b> The uncertainty of the next US observation <b>(I)</b>, the time constant of fear memory decline <b>(J)</b>, the relative fear-related neural activity at the conclusion of extinction <b>(K)</b> and the learning signal received by the extinction neural unit at the beginning of extinction <b>(L)</b> vary with the probability of the US. The time constant <b>(J)</b> was evaluated by fitting time course of the fear neural unit activity during extinction with <i>F = F</i>_<i>1</i>exp(<i>-t/τ</i>)+<i>F</i>_<i>0</i>, where <i>F</i>_<i>0</i> and <i>F</i>_<i>1</i> indicate positive constants, and <i>t</i> and <i>τ</i> indicate the number of extinction trials and the time constant, respectively.</p