Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats

Diederich, Kai; Koch, Michael

doi:10.1007/s00213-004-2052-y

Cited by 47 publications

(30 citation statements)

References 25 publications

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“…Interestingly, it was recently shown that PPTg-targeting GABAergic neurons in the LGP are activated at both prepulse and prepulse + pulse (PPI) conditions, and that transient inactivation of this region by lidocaine decreases PPI in mice. Furthermore, infusions of both GABA A and GABA B receptor antagonists into the PPTg decrease PPI, suggesting that the LGP regulates PPI by acting on GABA receptors in the PPTg (Diederich and Koch, 2005;Takahashi et al, 2007). Thus, it is possible that systemic (but not prefrontal) injections of baclofen used in this study, affects PPTg in the opposite direction, thereby causing an increase in basal PPI.…”

Section: Regional Effects Of Baclofenmentioning

confidence: 86%

Prefrontal GABAB Receptor Activation Attenuates Phencyclidine-Induced Impairments of Prepulse Inhibition: Involvement of Nitric Oxide

Fejgin

Pålsson

Wass

et al. 2009

Neuropsychopharmacol

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Recent theories propose that both GABA and glutamate signaling are compromised in patients with schizophrenia. These deficits can be observed in several brain regions including the prefrontal cortex (PFC), an area extensively linked to the cognitive dysfunction in this disease and notably affected by NMDA receptor antagonists such as phencyclidine (PCP). We have previously demonstrated that inhibition of the nitric oxide (NO) pathways in the brain, particularly in the PFC, prevents a wide range of PCP-induced behavioral deficits including disruption of prepulse inhibition (PPI). This study investigated the role of GABA(B) receptor signaling and NO in the effects of PCP on PPI. Mice received systemic or prefrontal injections of the GABA(B) receptor agonist baclofen (2.5-5 mg/kg and 1 mM) before PCP treatment (5 mg/kg) and were thereafter tested for PPI. GABA/NO interactions were studied by combining baclofen and the NO synthase inhibitor L-NAME (20 mg/kg) in subthreshold doses. The role of GABA(B) receptors for NO production in vivo was assessed using NO-sensors implanted into the rat PFC. PCP-induced PPI deficits were attenuated in an additive manner by systemic baclofen treatment, whereas prefrontal microinjections of baclofen completely blocked the effects of PCP, without affecting PPI per se. The combination of baclofen and L-NAME was more effective in preventing the effects of PCP than any compound by itself. Additionally, baclofen decreased NO release in the PFC in a dose-related manner. This study proposes a role for GABA(B) receptor signaling in the effects of PCP, with altered NO levels as a downstream consequence. Thus, prefrontal NO signaling mirrors an altered level of cortical inhibition that may be of importance for information processing deficits in schizophrenia.

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Section: Regional Effects Of Baclofenmentioning

confidence: 86%

Prefrontal GABAB Receptor Activation Attenuates Phencyclidine-Induced Impairments of Prepulse Inhibition: Involvement of Nitric Oxide

Fejgin

Pålsson

Wass

et al. 2009

Neuropsychopharmacol

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“…3B). This is interesting, since a previous study using pharmacological inactivation of the pedunculopontine tegmental nucleus (PPN) shows that the reduction of PPI after blocking neurotransmission in this nucleus is more pronounced at ISIs of 100 and 520 ms than at 25 and 1020 ms (Diederich and Koch 2004). Since the PPN is a key element of the cortico-limbic striatopallidotegmental circuit that mediates and regulates PPI Fendt et al 2001) it was concluded that PPI after very short and very long ISIs might recruit different brain circuits.…”

Section: Discussionmentioning

confidence: 97%

Selective Breeding of Reduced Sensorimotor Gating in Wistar Rats

2007

Self Cite

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Prepulse inhibition (PPI) of startle is an operational measure of sensorimotor gating that is reduced in some neuropsychiatric disorders (e.g. schizophrenia). Animal models have revealed insight into the neuronal and pharmacological underpinnings of PPI-deficits. Recent work has shown that a PPI-deficit can be selectively bred in Wistar rats and is already stable in the second filial generation. We here report on developmental and parametric characteristics of sensorimotor gating deficits in the 4th and 6th filial generation of male rats selectively bred for low PPI (low PPI) compared to rats with normal levels of PPI (high PPI). Low PPI rats showed significantly reduced PPI and variable startle magnitude (in pulse alone trials) along with reduced short-term habituation of startle as adults. Reduced PPI in the low PPI rats was found throughout development (tested on postnatal days 21, 35, 49, 70). PPI-deficits in the low PPI rats were evident at prepulse intensities ranging from 62-86 dB and for interstimulus intervals ranging between 30-1000 ms. These behavioral data add to a growing body of knowledge about the genetic basis of sensorimotor gating deficits and suggest that low PPI rats have potential use as an intermediate phenotype in schizophrenia research. The stable phenotype of breeding-induced PPI-deficits and reduced startle habituation indicates that PPI has strong genetic determinants and that selectively bred rats can be used for future neurophysiological, anatomical, pharmacological, and genomic analyses.

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“…The acoustic activation could either result from the distinct hissing tone caused by the air puffs leaving the Teflon tubes or from the primary visual activation via crossmodal activation through the somatosensory stimulus [Diederich and Koch, 2005;Lugo et al, 2008;McDowell et al, 2006;Senkowski et al, 2008;Diederich and Colonius, 2008].…”

Section: Discussionmentioning

confidence: 99%

Electrophysiology meets fMRI: Neural correlates of the startle reflex assessed by simultaneous EMG–fMRI data acquisition

Neuner¹,

Stöcker²,

Kellermann³

et al. 2010

Human Brain Mapping

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The startle reflex provides a unique tool for the investigation of sensorimotor gating and information processing. Simultaneous EMG-fMRI acquisition (i.e., online stimulation and recording in the MR environment) allows for the quantitative assessment of the neuronal correlates of the startle reflex and its modulations on a single trial level. This serves as the backbone for a startle response informed fMRI analysis, which is fed by data acquired in the same brain at the same time. We here present the first MR study using a single trial approach with simultaneous acquired EMG and fMRI data on the human startle response in 15 healthy young men. It investigates the neural correlates for isolated air puff startle pulses (PA), prepulse-pulse inhibition (PPI), and prepulse facilitation (PPF). We identified a common core network engaged by all three conditions (PA, PPI, and PPF), consisting of bilateral primary and secondary somatosensory cortices, right insula, right thalamus, right temporal pole, middle cingulate cortex, and cerebellum. The cerebellar vermis exhibits distinct activation patterns between the startle modifications. It is differentially activated with the highest amplitude for PPF, a lower activation for PA, and lowest for PPI. The orbital frontal cortex exhibits a differential activation pattern, not for the type of startle response but for the amplitude modification. For pulse alone it is close to zero; for PPI it is activated. This is in contrast to PPF where it shows deactivation. In addition, the thalamus, the cerebellum, and the anterior cingulate cortex add to the modulation of the startle reflex.

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Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats

Abstract: These findings suggest that GABAergic neurotransmission in the PPTg plays an important role for sensorimotor gating at intermediate ISIs and for response selection under demanding schedules of reinforcement.

Cited by 47 publications

References 25 publications

Prefrontal GABAB Receptor Activation Attenuates Phencyclidine-Induced Impairments of Prepulse Inhibition: Involvement of Nitric Oxide

Prefrontal GABAB Receptor Activation Attenuates Phencyclidine-Induced Impairments of Prepulse Inhibition: Involvement of Nitric Oxide

Selective Breeding of Reduced Sensorimotor Gating in Wistar Rats

Electrophysiology meets fMRI: Neural correlates of the startle reflex assessed by simultaneous EMG–fMRI data acquisition

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