Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis

Sarah Hescham, Yasin Temel, Sandra Schipper, Mélanie Lagiere, Lisa-Maria Schönfeld, Arjan Blokland, Ali Jahanshahi

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Abstract

Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

Original languageEnglish
Pages (from-to)1069–1075
Number of pages7
JournalBrain Structure & Function
Volume222
Issue number2
Early online date1 Feb 2016
DOIs
Publication statusPublished - Mar 2017

Keywords

  • Deep brain stimulation
  • Fornix
  • Memory
  • Hippocampus
  • Neurogenesis
  • PSYCHIATRIC-DISORDERS
  • ALZHEIMERS-DISEASE
  • DENTATE GYRUS
  • NEURONS
  • POTENTIATION

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