Neuromodulatory Role of Serotonin in the Ferret Thalamus

Abstract

Serotonergic fibers broadly innervate the thalamus and may influence the sleep wake cycle, attention, and other processes through modulation of neurons in this structure. However, the actions of serotonin in the dorsal thalamus have been investigated in detail only in the dorsal lateral geniculate nucleus. In the present study, we examined the action of serotonin in several different regions of the ferret dorsal thalamus, including the associative nuclei, using the in vitro slice preparation and intracellular recording techniques. In nearly all nuclei examined, the predominant action of serotonin was one of hyperpolarization and inhibition of the tonic firing mode. The magnitude of the hyperpolarizing response decreased with age and varied greatly across and somewhat within nuclei maintaining the following relationship (in descending order of magnitude): lateral posterior, lateral dorsal, pulvinar, mediodorsal, center median, anteroventral, central lateral, ventral basal, and medial geniculate. This hyperpolarization is elicited through two mechanisms: one direct and the other via local interneurons. The direct action occurs through an increase in potassium conductance mediated through the 5-HT(1A) receptor. This conclusion is supported by the findings that it persists in the presence of tetrodotoxin and block of GABAergic synaptic transmission, the reversal potential shifts in a Nernstian fashion with changes in extracellular potassium concentration, and the response is antagonized by the 5-HT(1A) antagonist WAY100635 and mimicked by the application of the 5-HT(1A)-selective agonist 8-OH DPAT. The second mechanism by which 5-HT evoked a hyperpolarization was through the activation of local interneurons. In slices in which GABA receptors were not blocked, 5-HT application increased the frequency and amplitude of spontaneous inhibitory postsynaptic potentials (IPSPs) occurring in thalamocortical neurons. Application of 5-HT to physiologically or morphologically identified interneurons evoked a prolonged suprathreshold depolarization. Our results suggest that serotonergic inputs act differentially across the thalamus in a complex manner involving direct and indirect mechanisms. It appears that 5-HT has a greater direct postsynaptic inhibitory influence in the posterior, medial, and intralaminar nuclei than in the primary sensory nuclei.

MDMA (3,4-Methylenedioxymethamphetamine)-Mediated Distortion of Somatosensory Signal Transmission and Neurotransmitter Efflux in the Ventral Posterior Medial Thalamus

“…The current findings are consistent with the results from in vitro studies that suggest that 5-HT suppresses thalamocortical transmission (Pape and McCormick, 1989;McCormick and Pape, 1990;Monckton and McCormick, 2002). Our Fig.…”

“…It has been demonstrated in several species that 5-HT depresses thalamocortical transmission (Pape and McCormick, 1989;McCormick and Pape, 1990;Monckton and McCormick, 2002). Furthermore, in vivo iontophoretic 5-HT elevates spontaneous discharge and suppresses sensoryevoked discharge of rat somatosensory (Waterhouse et al, 1986) and visual cortical neurons (Waterhouse et al, 1990).…”

Central serotonin neurons are required for arousal to CO 2

“…Hypercapnia directly activates midbrain 5-HT neurons (11,36). 5-HT release within the thalamus leads to a change in thalamocortical rhythms from a bursting pattern to a tonic pattern (8,37). This coincides with a change from high-voltage low-frequency synchronized activity in the cortical electroencephalogram consistent with slow wave sleep to low-voltage high-frequency desynchronized activity consistent with W (8).…”

Serotonin increases synaptic activity in olfactory bulb glomeruli

“…Their firing rates are also modulated by state-dependent behavioral events such as reward and punishment (Jacobs and Azmitia 1992). Most studies of 5HT modulation have focused on higher brain areas such as cortex, but there is evidence for modulation of response properties in precortical areas, such as in thalamus (Monckton and McCormick 2002) and brainstem primary sensory nuclei (Depuy et al 1990;Ptak et al 2009). …”