Hippocampal neurotrophins after stimulation of the basolateral amygdala, and memory improvement in lesioned rats

Abstract

Purpose: To investigate a possible role of neurotrophins in the memory improving effect of stimulating the basolateral amygdala. Methods: The BDNF and NGF levels were measured in the hippocampus of fimbria-fornix lesioned male rats after four days of training in the water maze and stimulation of the basolateral amygdala. Results: The behavioral results confirm that daily post-training stimulation of the amygdala improves the learning abilities of the lesioned animals. BDNF increased in lesioned and trained animals, but stimulating the basolateral amygdala induces a significantly greater increase. NGF showed a slight (but significant) increase in fimbria-fornix lesioned and trained animals, but stimulating the amygdala does not produce a further increase. In separate groups of animals we measured the levels of both neurotrophins in acute experiments, after 2 and 24 hours of stimulating the amygdala. BDNF was significantly increased at both times, while NGF showed again only slight increases (significant at 24 h). Conclusions: These results suggest that the BDNF response to amygdala stimulation might be of functional importance in the observed learning improvement. The changes in NGF are most likely due to the accumulation of this protein after removal of the septal axons.

Amygdala stimulation ameliorates memory impairments and promotes c‐Fos activity in fimbria‐fornix‐lesioned rats

“…The second experiment was performed in FF-lesioned rats, with or without BLA stimulation 15 min after finishing each day training session in the MWM. The behavioral results confirmed the findings reported in previous papers from our group (Merceron-Martinez et al, 2013;Merceron-Martinez et al, 2016): stimulating the amygdala after the training session partially reverts the severe learning impairment provoked by the lesion.…”

“…The data shown in the Figure 5 illustrate, in line with previous data from our group (Almaguer-Melian et al, 2005;Merceron-Martinez et al, 2013;Merceron-Martinez et al, 2016), that FF-lesion induces a severe and long-lasting impairment in task acquisition. However, the BLA daily post-training stimulation exerted a significant positive effect on the search patterns during acquisition and retention, as revealed by the longer time spent in target quadrant and the higher number of crossings during the probe trial.…”

“…In previous papers, we have provided consistent data that FF-lesion provokes an almost complete hippocampal cholinergic denervation (Almaguer-Melian et al, 2003;Almaguer-Melian et al, 2005;Almaguer-Melian et al, 2006;Almaguer-Melian et al, 2015;Jas, Almaguer, Frey, & Bergado, 2000;Merceron-Martinez et al, 2013;Merceron-Martinez et al, 2016;Mercerón-Martínez et al, 2018), which is evidenced by the loss of AChE staining. Additionally, lesioned animals display a severe impairment in spatial memory in the MWM, (Almaguer-Melian et al, 2003;Almaguer-Melian et al, 2005;Almaguer-Melian et al, 2015;de Bruin, Moita, de Brabander, & Joosten, 2001;Cassel et al, 1998;Merceron-Martinez et al, 2013;Merceron-Martinez et al, 2016;Mercerón-Martínez et al, 2018). Interestingly, FF-lesion also affects Long-Term Potentiation (LTP), which is considered a cellular model for memory (Bergado, Moreno, & Nuñez, 1996;Bergado, Moreno, Soto, Castellano, & Castillo, 1997;Buzsáki and Gage, 1989).…”

“…Despite this, the stimulation of the BLA improves memory acquisition in the Morris Water Maze (MWM) of FF‐lesioned animals (Almaguer‐Melian et al, 2005). This effect is mild, but consistently replicated it in several studies (Merceron‐Martinez et al, 2013; Merceron‐Martinez et al, 2016; Mercerón‐Martínez, Almaguer‐Melian, Alberti‐Amador, & Bergado, 2018). This memory improving the effect of post‐training BLA stimulation involves an increased transcription and translation of the bdnf and arc genes at the DG and prefrontal cortex (Merceron‐Martinez et al, 2013; Merceron‐Martinez et al, 2016).…”

“…This effect is mild, but consistently replicated it in several studies (Merceron‐Martinez et al, 2013; Merceron‐Martinez et al, 2016; Mercerón‐Martínez, Almaguer‐Melian, Alberti‐Amador, & Bergado, 2018). This memory improving the effect of post‐training BLA stimulation involves an increased transcription and translation of the bdnf and arc genes at the DG and prefrontal cortex (Merceron‐Martinez et al, 2013; Merceron‐Martinez et al, 2016). Along these functional changes, also mechanisms of morphological plasticity are involved, as suggested by the increased expression of the axon growth‐related protein GAP‐43, and the dendritic MAP‐2 (Mercerón‐Martínez et al, 2018).…”