Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: A retro‐ and antero‐grade transport and immunohistochemical study

Abstract

Increasingly strong evidence suggests that cholinergic neurons in the mesopontine tegmentum play important roles in the control of wakefulness and sleep. To understand better how the activity of these neurons is regulated, the potential afferent connections of the laterodorsal (LDT) and pedunculopontine tegmental nuclei (PPT) were investigated in the rat. This was accomplished by using retrograde and anterograde axonal transport methods and NADPH-diaphorase histochemistry. Immunohistochemistry was also used to identify the transmitter content of some of the retrogradely identified afferents. Following injections of the retrograde tracer wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) into either the LDT or the PPT, labelled neurons were seen in a number of limbic forebrain structures. The medial prefrontal cortex and lateral habenula contained more retrogradely labelled neurons from the LDT, whereas in the bed nucleus of the stria terminalis and central nucleus of the amygdala, more cells were labelled from the PPT. Moderate numbers of neurons were seen in the magnocellular regions of the basal forebrain, and many labelled neurons were observed in the lateral hypothalamus, the zona incerta, and the midbrain central gray from both the LDT and the PPT. Accessory oculomotor nuclei in the midbrain as well as eye movement-related structures in the lower brainstem contained some neurons labelled from the LDT, and fewer neurons from the PPT. A few labelled neurons were seen in somatosensory and other sensory relay nuclei in the brainstem and the spinal cord. Retrograde labelling was seen in a number of extrapyramidal structures, including the globus pallidus, entopenduncular and subthalamic nuclei, and substantia nigra following PPT injections; with LDT injections, labelling was similar in density in the substantia nigra but virtually absent in the entopeduncular and subthalamic nuclei. Data with the fluorescent retrograde tracer fluorogold combined with immunofluorescence indicated that many neurons in the zona incerta-lateral hypothalamic region that were retrogradely labelled from the LDT contained alpha-melanocyte-stimulating hormone. Numerous neurons were labelled throughout the reticular formation of the brainstem following either LDT or PPT injections. Many neurons retrogradely labelled in the LDT and PPT, the dorsal and median raphe nuclei, and the locus ceruleus contained choline acetyltransferase, serotonin, and tyrosine hydroxylase, respectively. The anterograde tracers WGA-HRP and phaseolus vulgaris leucoagglutinin were used to confirm some of the projections indicated by the retrograde labelling data; anterograde labelling was seen in the LDT and PPT following injections of one of these tracers into the medial prefrontal cortex, lateral hypothalamus, and the contralateral LDT.(ABSTRACT TRUNCATED AT 400 WORDS)

The Hippocampus Modulates Dopamine Neuron Responsivity by Regulating the Intensity of Phasic Neuron Activation

“…Thus, vSub activation excites Acb projection neurons that inhibit ventral pallidal GABAergic afferents to the VTA, thereby releasing DA neurons from a tonic inhibitory influence (Floresco et al, 2001). In contrast, the pedunculopontine tegmental nucleus (PPTg) is a glutamatergic/cholinergic region driven by a number of limbic afferents, including the prefrontal cortex, bed nucleus of the stria terminalis and central nucleus of the amygdala (Semba and Fibiger, 1992), and has been shown to be activated by auditory (Pan and Hyland, 2005;Reese et al, 1995), visual (Pan and Hyland, 2005) and somatosensory stimuli (Grunwerg et al, 1992). The PPTg was found to also directly regulate burst firing of DAergic neurons (Floresco et al, 2001;Lokwan et al, 1999).…”

High-Frequency Afferent Stimulation Induces Long-Term Potentiation of Field Potentials in the Ventral Tegmental Area

“…Both neuron types project to the nucleus accumbens and to the prefrontal cortex, although GABA neurons in the VTA also act locally to inhibit VTA dopamine neurons (Carr and Sesack, 2000a;Svingos et al, 2001). Excitatory afferents to the VTA include direct glutamatergic inputs from prefrontal cortex, laterodorsal tegmental nucleus, lateral hypothalamus, and bed nucleus of the stria terminalis (Semba and Fibiger, 1992;Garzon et al, 1999;Carr and Sesack, 2000b;Georges and Aston-Jones, 2001). Stimulation of excitatory afferents in the VTA activates both postsynaptic AMPA receptors and NMDA receptors.…”

From synapse to gene product: prolonged expression of c-fos induced by a single microinjection of carbachol in the pontomesencephalic tegmentum

“…The specificity of the cellular response lies within the type of cell itself, and different target genes may be selected for regulation by c-fos in neurons of different neurotransmitter signatures [57]. Indeed, the rostral PMT cell groups of the LDT/PPT and the caudal PMT cell group of the PBN show a marked heterogeneity in PGO bursting properties and neurotransmitter populations [15,41,54,70,71,79,80,86]. We have taken an interest in these neurons and have shown that while cholinoceptive injection sites in the caudolateral PMT primarily receive cholinergic afferents from the LDT/PPT, non-cholinergic populations provide the greatest proportion of afferents [68].…”

“…Neurons within this region have been extensively studied for their executive role in sleep-wake behavioral state control [1,78] and have been shown to be a source of net excitatory drive with reciprocal connections to cholinergic cell groups of the PMT [44,80]. Our recent anatomical studies of LDT/PPT neurons during LTPE reveal the presence of cholinergic, gamma-amino-butyric acid (GABA)-ergic, and glutamatergic transmitter phenotypes [29] and reciprocity between Fos-IR projection neurons and injection sites in the caudolateral PMT [30].…”