Article

When is adult hippocampal neurogenesis necessary for learning? Evidence from animal research

Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Campus de Teatinos, E-29071 Málaga, Spain.
Reviews in the neurosciences (Impact Factor: 3.31). 01/2011; 22(3):267-83. DOI: 10.1515/RNS.2011.027
Source: PubMed

ABSTRACT The hippocampus is a key brain structure involved in the short- and long-term processing of declarative memory. Since adult hippocampal neurogenesis was first found, numerous studies have tried to establish the contribution of newborn neurons to hippocampus-dependent cognitive functions. However, this large amount of research has generated contradictory results. In this paper, we review the body of evidence investigating the relationship between hippocampal neurogenesis and learning to conclude the functional role of adult-born hippocampal neurons. First, factors that could explain discrepancies among experiments are taken into account. Then, in addition to methodological differences, we emphasize the importance of the age of the newborn neurons studied, as to how their maturation influences both their properties and potential functionality. Next, we discuss which declarative memory components could require involvement of adult hippocampal neurogenesis, taking into consideration the representational demands of the task, its difficulty and the level of performance reached by the subject. Finally, other factors that could modulate neurogenesis and memory, such as stress levels or previous experience of the animal, should also be taken into consideration in interpreting experiments focused on neurogenesis. In conclusion, our analysis of published studies suggests that new adult-born neurons, under certain circumstances, have a crucial and irreplaceable role in hippocampal learning.

1 Follower
 · 
184 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although adolescence is a common age to initiate alcohol consumption, the long-term consequences of exposure to alcohol at this time of considerable brain maturation are largely unknown. In studies utilizing rodents, behavioral evidence is beginning to emerge suggesting that the hippocampus may be persistently affected by repeated ethanol exposure during adolescence, but not by comparable alcohol exposure in adulthood. The purpose of this series of experiments was to explore a potential mechanism of hippocampal dysfunction in adults exposed to ethanol during adolescence. Given that disruption in adult neurogenesis has been reported to impair performance on tasks thought to be hippocampally related, we used immunohistochemistry to assess levels of doublecortin (DCX), an endogenous marker of immature neurons, in the dentate gyrus (DG) of the hippocampus 3-4 weeks after adolescent (postnatal day, PD28-48) or adult (PD70-90) intermittent ethanol exposure to 4 g/kg ethanol administered intragastrically. We also investigated another neurogenic niche, the subventricular zone (SVZ), to determine if the effects of ethanol exposure were region specific. Levels of cell proliferation and cell death were also examined in the DG via assessing Ki67 and cleaved caspase-3 immunoreactivity, respectively. Significantly less DCX was observed in the DG of adolescent (but not adult) ethanol-exposed animals about 4 weeks after exposure when these animals were compared to control age-mates. The effects of adolescent ethanol on DCX immunoreactivity were specific to the hippocampus, with no significant exposure effects emerging in the SVZ. In both the DG and the SVZ there was a significant age-related decline in neurogenesis as indexed by DCX. The persistent effect of adolescent ethanol exposure on reduced DCX in the DG appears to be related to significant increases in cell death, with significantly more cleaved caspase-3-positive immunoreactivity observed in the adolescent ethanol group compared to controls, but no alterations in cell proliferation when indexed by Ki67. These results suggest that a history of adolescent ethanol exposure results in lowered levels of differentiating neurons, probably due at least in part to increased cell death of immature neurons. These effects were evident in adulthood, weeks following termination of the chronic exposure, and may contribute to previously reported behavioral deficits on hippocampal-related tasks after chronic ethanol exposure in adolescence. © 2014 S. Karger AG, Basel.
    Developmental Neuroscience 06/2014; 36(3-4). DOI:10.1159/000362874 · 2.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. © 2015 Society for the Study of Addiction.
    Addiction Biology 04/2015; DOI:10.1111/adb.12248 · 5.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Se reconoce que el ejercicio puede aumentar la neurogénesis adulta y este fenómeno podría evidenciarse en diferentes niveles (comportamental, celular, electrofisiológico). El objetivo del estudio fue evaluar el efecto de la estimulación de la neurogénesis hipocampal mediante el ejercicio, sobre la memoria de trabajo evaluada mediante una tarea de laberinto en T en ratas macho adultas de la sepa Wistar. Se utilizó un diseño experimental de dos grupos en el cual un grupo experimental GE (n = 12) fue sometido a un programa de ejercicio forzado durante 5 días, al mismo tiempo que se administró un marcador de síntesis de ADN (Bromo-deoxi-uridina [BrdU](50 mg/kg IP.), los animales control GC (n = 9) no fueron expuestos al ejercicio pero se les administró igual dosis de BrdU. Tres (3) animales (GE = 2; GC = 1) se sometieron a cirugía de implantación de electrodos en la corteza frontal medial (+3,0 mm AP; ± 0.5 mm ML; -3.0mm DV) e hipocampo (-3.0mm AP; ± 1.8mm ML; -3.5mm DV) para registro electroencefalográfico durante la ejecución en el laberinto en T. 6-8 semanas después de la aplicación del ejercicio se evaluó la memoria de trabajo en laberinto en T y se analizaron cuatro (4) días de elección evaluando la alternancia de las opciones como indicador de memoria de trabajo. No se encontró diferencia comportamental entre los grupos experimental y control en variables comportamentales (alternancia, índice de preferencia, tiempo de respuesta, tiempo de ensayo, consumo de comida). El registro electroencefalográfico de los animales no mostró una tendencia a la coherencia entre las áreas registradas, siendo éste un indicador fisiológico del proceso de elección. En cuanto a la cantidad de nuevas neuronas no se encontraron diferencias por grupos.
    12/2014, Degree: Master, Supervisor: Fernando Cardenas; Manuel Rojas

Full-text

Download
11 Downloads
Available from
Apr 9, 2015