Excitotoxic lesions of the pedunculopontine tegmental nucleus in rats impair performance on a test of sustained attention

Abstract

Recent research has suggested that the pontomesencephalic tegmentum might be an important part of a network underlying sustained attention. The largest structure of the pontomesencephalic tegmentum is the pedunculopontine tegmental nucleus, which has ascending connections to thalamus and with corticostriatal systems. In this experiment we examined the performance of rats following bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on a test of sustained attention previously used to examine frontal cortical function. After an initial period of darkness, the rats had to attend continuously to a dim stimulus light that would, at unpredictable intervals, become transiently brighter. During this period of increased stimulus brightness the rats could press a lever to obtain a food reward. Rats were trained to a criterion level of performance before lesions were made. After surgery, sham lesioned rats (n=7) resumed accurate responding, with an average successful detection rate of approximately 70%. Pedunculopontine lesioned rats (n=7), however, only achieved a successful detection rate of approximately 40%. When the duration of the bright target stimulus was increased from 1.5 to 4 s, the performance of the pedunculopontine lesioned rats significantly improved. The observation that an increase in brightness duration caused a marked improvement in lesioned rats' performance suggests strongly that the impairment was in attention rather than motor ability or simple sensory processing. These data are taken to be consistent with the hypothesis that the pedunculopontine tegmental nucleus is an important part of a network maintaining attention.

Deficit in sustained attention following selective cholinergic lesion of the pedunculopontine tegmental nucleus in rat, as measured with both post-mortem immunocytochemistry and in vivo PET imaging with [18F]fluoroethoxybenzovesamicol

“…This clearly indicates that the absence of deficit in the easier version was not simply due to improvement over time. It seems therefore that the PPTg cholinergic system plays a primary role in sustained attention, a finding that confirms other results [14,15] obtained with non-selective lesions of the PPTg and other tasks of attention.…”

“…In this respect, it should be stressed that the cholinergic neurons of the basal forebrain (Ch4) have also been found to be involved in sustained attention [50,51]. As pointed out by Kozak et al [14] it is possible that both PPTg and the basal forebrain are two components of a distributed network, both serving to control common output processes such as the regulation of thalamocortical tonic activity, or the adjustment of cortical signal-to-noise ratio. Alternatively, the network could be represented as having a rather more sequential organization, where the PPTg would be activated before the basal forebrain.…”

“…Such perspective comes from animal studies showing that PPTg lesions may induce deficits in tasks requiring alertness and attention [12][13][14][15]. However, PPTg lesions in these studies were achieved mostly by using unspecific excitotoxins such as ibotenic or quisqualic acids, which are known to affect both cholinergic and non-cholinergic neurons.…”

How best to consider the structure and function of the pedunculopontine tegmental nucleus: Evidence from animal studies

“…Nevertheless there are important functional data to consider. Experiments examining rats bearing bilateral excitotoxic lesions of the PPTg have shown deficits in attentional performance, using either the five choice serial reaction time task [198] or a simple attentional task [199] developed by Granon and her colleagues [200] to examine the role of the prefrontal cortex in sustained attention. These studies are consistent both with the notion that the PPTg has a role to play in gating incoming sensory data [201], and that the PPTg has a role to play in prepulse inhibition of the startle reflex [202,203].…”

Critical evaluation of the anatomical location of the Barrington nucleus: Relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus

“…In animal models, PPN lesions have been reported to impair attention, executive function, working memory and learning Inglis et al, 2000Inglis et al, , 2001Inglis and Winn 1995;Kozak et al, 2005;Garcia-Rill, 1991). High frequency PPN DBS in a non-human primate model had similar effects.…”