Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices

Abstract

Despite its predominant role in the peripheral nervous system and particularly at the motor endplate where it was first discovered, fast nicotinic cholinergic transmission has been found up to now only exceptionally in the central nervous system. One classic example is the synaptic activation of the Renshaw cell in the spinal cord, which receives a cholinergic nicotinic input from motoneurones (Eccles et al. 1954). Similarly, synaptic nicotinic potentials have been reported in brainstem vagal motoneurones (Zhang et al. 1993) and neuronal nicotinic acetylcholine receptor (nAChR) mediated responses could at least in part mediate dopamine release in the striatum (Clarke et al. 1987; Futami et al. 1995). So far, however, there has been no report of fast cholinergic transmission in mammalian cortical regions. Contrasting with this, nicotine has been shown to play a major role in modulating brain functions (Wonnacott, 1997). Recent developments in gene technology have revealed the presence in many brain areas of mRNA coding for different nicotinic receptor subtypes (Goldman et al. 1987;Sargent, 1993). Furthermore, the presence of these mRNAs correlates well with reports of the existence of specific binding sites for both ACh analogues and the selective nicotinic receptor antagonist á_bungarotoxin (á-BgTX;Clarke et al. 1985). In addition, electrophysiological studies made on dissociated hippocampal neurones have demonstrated the existence of functional nicotinic receptors and identified several types of nicotinic currents (Alkondon & Albuquerque, 1993; Albuquerque et al. 1997). Finally, strong evidence implicates nicotinic acetylcholine receptors in behaviour, learning and memory as well as in the reinforcing actions of nicotine (Role & Berg, 1996;Picciotto et al. 1998). A major issue, therefore, has been to understand whether neuronal nAChRs have purely a modulatory role, representing mainly targets for the low concentrations of nicotine that reach the brain during smoking, or whether, as found in the peripheral nervous system, they also mediate fast synaptic transmission. This is not unlikely considering the evidence showing the existence in the hippocampus of a

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

“…The postsynaptic response is mediated by ␣4␤2-like nAChRs (Dourado and Sargent, 2002). Other examples have now emerged, documenting nicotinic postsynaptic responses involving both ␣7-and non-␣7 nAChRs in the CNS (Zhang et al, 1993;Roerig et al, 1997;Alkondon et al, 1998;Frazier et al, 1998, Hefft et al, 1999Jones et al, 1999). Ultrastructural studies have confirmed that at least ␣4␤2-nAChRs can be found in PSDs in the rat substantia nigra (Arroyo-Jimenez et al, 1999).…”

Cholinergic interneuron characteristics and nicotinic properties in the striatum

“…The synapses formed by cholinergic neurons onto spiny neurons have not been shown to generate synaptic currents by way of ionotropic nicotinic receptors, but act primarily in a modulatory fashion (Uchimura and North, 1990;Howe and Surmeier, 1995;Galarraga et al, 1999;Gabel and Nisenbaum, 1999;Calabresi et al, 2000). It is possible, however, that a small excitatory synaptic response mediated by nAChRs has gone undetected and could contribute to the modulatory cholinergic action, as is the case in the hippocampus (Alkondon et al, 1998;Frazier et al, 1998;Hefft et al, 1999). Spiny neurons do express muscarinic m1 and sometimes m4 receptors (Hersch et al, 1994;Alcantara et al, 2001;Yan et al, 2001) that modulate voltage-gated channels.…”

Cellular and synaptic mechanisms of nicotine addiction

“…Prolonged exposure to low concentrations of nicotine decreases the ACh sensitivity of the GABAergic input to interneurons. Hippocampal interneurons are one of the few cell types that have been shown to receive cholinergic synaptic input mediated by nAChRs (Frazier et al, 1998a;Hefft et al, 1999). It will be interesting to learn more about nicotine's effects on the contribution of these neurons to the circuitry of the hippocampus.…”