Awarded by ATS at Society for Neuroscience (SFN) New Orleans, Louisiana • November 8-12, 2003
Be sure to check out the cover article contributed by Dr. McGaughy in Targeting Trends newsletter (First Quarter, 2004).
425.4 CHOLINERGIC DEAFFERENTATION OF THE ENTORHINAL CORTEX IN RATS IMPAIRS ENCODING OF NOVEL BUT NOT FAMILIAR STIMULI IN A DELAYED NON-MATCH TO SAMPLE TASK (DNMS).
J.A.McGaughy; M.Jindal; H.B.Eichenbaum; M.E.Hasselmo
featuring IT-01 192-IgG-SAP (poster)
Muscarinic cholinergic receptor activation in entorhinal cortex (EC) activates intrinsic depolarizing membrane currents which cause self-sustained spiking activity in single neurons (Klink and Alonso, J. Neurophys. 77, 1997). This effect may underlie delay activity and match-dependent activity changes in delayed match to sample tasks (Fransen et al., J. Neurosci. 22, 2002) and could allow accurate maintenance of novel information without dependence on synaptic modification associated with previous exposure (familiarization). Consistent with this, research in human subjects suggest that the medial temporal lobes are specifically activated during working memory for novel but not familiar stimuli (Stern, et al. Hippocampus v. 11, 2001), and cholinergic deafferentation of the rhinal cortex in non-human primates has been shown to impair memory for trial-unique (novel) stimuli (Turchi et al., SFN abstracts v. 28). The current study tests the hypothesis that cholinergic deafferentation of the EC produces impairments in working memory for novel but not familiar stimuli. Prior to surgery rats were trained in an odor DNMS task with a brief delay. After reaching asymptotic performance, rats were infused with either 192-IgG-saporin (SAP) or its vehicle into the EC (0.01 µg/µl; 1.0 µl/injection; 6 infusions/hemisphere). Rats were not impaired at any delay when tested with familiar odors but showed significant, persistent impairments when tested with novel odors. An increase in task difficulty alone was insufficient to explain these effects. These data support the hypothesis that cholinergic afferents to the EC activate cellular mechanisms of sustained spiking activity necessary for maintenance of novel but not familiar stimuli in a working memory task.
Support Contributed By: NIH MH61492, MH60013, DA16454.