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

Abstract

It is not known how the brain modifies its regulatory systems in response to the application of a drug, especially over the long term of weeks and months. We have developed a model system approach to this question by manipulating cholinergic cell groups of the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei in the pontomesencephalic tegmentum (PMT), which are known to be actively involved in the timing and quantity of rapid eye movement (REM) sleep. In a freely moving feline model, a single microinjection of the cholinergic agonist carbachol conjugated to a latex nanosphere delivery system into the caudolateral PMT elicits a long-term enhancement of one distinguishing phasic event of REM sleep, ponto-geniculo-occipital (PGO) waves, lasting 5 days but without any significant change in REM sleep or other behavioral state. Here, we test the hypothesis that cholinergic activation within the caudolateral PMT alters the postsynaptic excitability of the PGO network, stimulating the prolonged expression of c-fos that underlies this long-term PGO enhancement (LTPE) effect. Using quantitative Fos immunohistochemistry, we found that the number of Fos-immunoreactive (Fos-IR) neurons surrounding the caudolateral PMT injection site decreased sharply by postcarbachol day 03, while the number of Fos-IR neurons in the more rostral LDT/PPT increased >30-fold and remained at a high level following the course of LTPE. These results demonstrate a sustained c-fos expression in response to pharmacological stimulation of the brain and suggest that carbachol's acute effects induce LTPE via cholinergic receptors, with subsequent transsynaptic activation of the LDT/PPT maintaining the LTPE effect.

Neonatal handling on the first postnatal day leads to increased maternal behavior and fos levels in the brain of the newborn rat

“…However there are reports of delayed and/ or protracted Fos expression (Quattrochi, Bazalakova, & Hobson, 2005;Xu, Zheng, Ho, & Qian, 2006). It is noteworthy that the latter involve plasticity-related longterm changes in brain function, as is the case for the effects of ''neonatal handling.…”

The Neurobiology of Sleep

“…Destruction of these nuclei blocks these waves. [108][109][110] More extensive Fos mapping has been done to identify neurons activated during REM sleep in the rat. Verret et al 111 found that only a few cholinergic neurons from the laterodorsal and pedunculopontine tegmental nuclei were Fos-labeled after REM sleep.…”

Social contact elicits immediate-early gene expression in dopaminergic cells of the male prairie vole extended olfactory amygdala

“…Because the formation of partner preferences in male prairie voles requires rather long sexual interactions with a female (up to 24 h, Insel et al, 1995, Winslow et al, 1993), and surprisingly prolonged Fos expression can be seen after acute or chronic social or other stimulation (Bullitt et al, 1992, Matsuda et al, 1996, Quattrochi et al, 2005, Ricci et al, 2007, Stack and Numan, 2000, Wrynn et al, 2000, Xu et al, 2006), we also examined Fos expression in TH-ir cells of the pBST and MeApd after males cohabitated with a sexually receptive female for 6 or 24 hr.…”