Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro

Abstract

The actions of ACh in the medial habenular nucleus (MHb) were investigated using extra- and intracellular recording techniques in guinea pig thalamic slice maintained in vitro. Applications of ACh to MHb neurons resulted in rapid excitation followed by inhibition. Neither of these responses was abolished by blockade of synaptic transmission, indicating that they are consequences of ACh action directly on MHb cells. Local applications of the nicotinic agonists nicotine and cytisine caused long-lasting excitation, while applications of another nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium caused both the excitatory and inhibitory responses. Applications of the muscarinic agonists DL-muscarine and acetyl-beta-methylcholine did not consistently cause either the excitatory or inhibitory response. Adding the nicotinic antagonist hexamethonium to the bathing medium blocked both the excitatory and inhibitory ACh responses, while addition of the muscarinic antagonists atropine or scopolamine had no effect. These results indicate that the effects of ACh on MHb neurons are mediated by nicotinic receptors. Intracellular recordings revealed that ACh or nicotine cause an increase in membrane conductance associated with depolarizations that had an average reversal potential of -16 to -11 mV. These results indicate that the ACh-induced excitation is due to an increase in membrane cation conductance. The inhibitory response that follows ACh-induced depolarization and repetitive firing was associated with a hyperpolarization and an increase in membrane conductance. Similar postexcitatory inhibition could also be elicited by direct depolarization or by applications of glutamate, indicating that the hyperpolarizing response to ACh may be an endogenous postexcitatory potential that is not directly coupled to activation of nicotinic receptors. These results suggest that cholinergic transmission in the MHb may be largely of the nicotinic type. This nucleus may be of one of the major regions of the nervous system through which nicotine mediates its central effects.

Ionic Mechanism of Long-Lasting Discharges of Action Potentials Triggered by Membrane Hyperpolarization in the Medial Lateral Habenula

“…In our recordings, most neurons in the medial nucleus of the habenula generate tonic series of spontaneous action potentials, whereas cells in the lateral part of the lateral habenula mostly generate burst discharges of action potentials (data not shown). These patterns of electrical activity are consistent with those reported in previous studies (McCormick and Prince, 1987;Wilcox et al, 1988;Huguenard et al, 1993). The medial part of the lateral habenula contains both types of neurons that generate action potentials in tonic and burst modes.…”

“…For example, the neurons in the medial habenular nucleus spontaneously generate tonic firing of action potentials (McCormick and Prince, 1987), whereas neurons in the lateral habenular nucleus produce spontaneous burst oscillations (Wilcox et al, 1988). These bursts of action potentials in the lateral habenular nucleus are mediated by the activation of low-threshold Ca 2ϩ current (Wilcox et al, 1988;Huguenard et al, 1993).…”

Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording

“…Desensitization is also characteristic of nicotinic responses (Katz & Thesleff, 1957). Block by hexamethonium is typical of nicotinic actions in ganglia (Paton & Zaimis, 1949) and brain (Egan & North, 1986;McCormick & Prince, 1987): its voltage-dependence (Figure 3b) has previously been shown in ganglion cells (Rang, 1982). The finding of voltage-dependent block by hexamethonium, along with the insensitivity of the response to TTX and cobalt, indicate that the response was due to direct activation of nicotinic receptors on VTA neurones.…”

Molecular and Functional Heterogeneity of Hyperpolarization-Activated Pacemaker Channels in the Mouse CNS

“…3F ), whereas mHCN1 and mHCN2 probes Olfactory bulb show little staining in this region. This observation is particularly interesting in view of the fact that medial habenula neurons are spontaneously active, firing in a regular 2-6 Hz repetitive manner, while completely lacking the low-threshold Ca conductance that often interacts with I h to generate spontaneous firing (McCormick and Prince, 1987). Both mHCN2 and mHCN4 are expressed in the lateral habenula (Fig.…”