Elsevier

Neuroscience

Volume 116, Issue 1, 15 January 2003, Pages 179-186
Neuroscience

Original contribution
Blockade of epinephrine priming of the cerebral auditory evoked response by cortical cholinergic deafferentation

https://doi.org/10.1016/S0306-4522(02)00702-9Get rights and content

Abstract

The present study tested hypotheses derived from a neurobehavioral model of anxiety that posits an important role of the basal forebrain cholinergic system in the cortical processing of anxiety-associated stimuli and contexts. We hypothesized that visceral afferent activity induced by systemic administration of epinephrine would enhance the processing of auditory stimuli as evidenced by the cerebral auditory evoked response. We further predicted that selective lesions of the basal forebrain cortical cholinergic projection system would disrupt this processing, and would further block the effects of epinephrine. Results confirmed these hypotheses. Epinephrine was found to enhance the amplitude of the P70 component of the auditory evoked response in rats. Selective lesions of the basal forebrain corticopetal cholinergic projection, by intrabasalis infusions of 192 IgG saporin, delayed and reduced the amplitude of the P70 component, and blocked the potentiating effects of epinephrine on the auditory evoked response.

The present results are consistent with the view that visceral afferent input may modulate cortical processing of sensory signals via the basal forebrain cholinergic system. These considerations emphasize the potential importance of ascending, bottom-up modulation of processing by telencephalic circuits that may impact on a wide range of behavioral functions.

Section snippets

Subjects

Subjects were adult male Sprague–Dawley rats (Harlan, Indianapolis, IN, USA), 90–120 days old at the time of surgery. Animals were housed in a temperature (73 °F) and humidity (45%) controlled colony on a 12:12 light/dark cycle (lights on a 6:30 AM). Food and water were available ad libitum. Animal care and use was in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and was approved by the Institutional Laboratory Animal Care and Use Committee

Histological results

As illustrated in Fig. 1, intra-basalis infusions of 192 IgG-saporin resulted in extensive cortical cholinergic deafferentation. Analysis of lesioned animals revealed greater than 95% loss of AChE-positive fibers bilaterally in most cortical areas, with almost no residual labeled fibers visible in the frontoparietal and temporal cortical regions (see Fig. 1). Similar to previous studies (e.g. McGaughy et al 1996, Turchi and Sarter 2000, the loss of cholinergic fibers in the cingulate,

Discussion

Results of the present study revealed that systemic epinephrine can modulate auditory processing as evidenced by an increase in amplitude of the major P70 component of the AER in control animals. Selective lesions of the basal forebrain cholinergic system were found to disrupt auditory processing as reflected in a delayed and attenuated P70. Finally, basal forebrain lesions were also found to block epinephrine enhancement of the AER. In view of the selectivity of the immunotoxin for basal

Acknowledgements

We thank Stephen J. McConoughey for assistance. This research was supported in part by a grant from the NHLBI (HL54428).

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