Effect of reversible inactivation of locus ceruleus on spatial reference and working memory

Neuroscience. 2009 Feb 18;158(4):1284-91. doi: 10.1016/j.neuroscience.2008.11.001. Epub 2008 Nov 7.

Abstract

The locus coeruleus (LC) is the largest source of norepinephrine (NE) in the prefrontal cortex and the hippocampus, influencing the cognitive functions of these areas. All previous studies have studied the role of the LC-NE system on learning and memory using the irreversible lesion technique, employing either electrocoagulation or excitotoxins. However, the reversible functional inactivation of LC by means of stereotaxic local microinjection of lidocaine could measure the phases of memory processing (acquisition, consolidation and retention) without any interference with the other cognitive functions of the same structure either during earlier or later phases of the same process. The aim of this study is to investigate LC involvement in spatial reference and working memory by inducing bilateral pre-training, post-training and pre-retrieval lidocaine functional inactivation using the Morris water maze task. The reversible inactivation of LC was applied at different stages of spatial memory formation: (1) immediately before the training sessions to determine the effects on acquisition of the both reference and working memory; (2) immediately after the training session to evaluate effects on both spatial memory consolidation and retention of working memory; and (3) immediately before the 24 h retention session to analyze the effects on the retrieval process of reference memory. Our results indicate that the bilateral reversible inactivation of LC significantly impaired the acquisition of reference and working memory, while it had no effect on consolidation and/or retention of such memories in the Morris water maze (MWM) task. Therefore, the noradrenergic system of the LC may play a more important role in acquisition than in consolidation and retrieval of spatial memory in wistar rats.

MeSH terms

  • Analysis of Variance
  • Anesthetics, Local / pharmacology
  • Animals
  • Escape Reaction / drug effects
  • Escape Reaction / physiology
  • Functional Laterality / drug effects
  • Functional Laterality / physiology
  • Lidocaine / pharmacology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology*
  • Microinjections / methods
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*

Substances

  • Anesthetics, Local
  • Lidocaine