Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

Abstract

Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

Figure 1

The major cholinergic afferent projections to the hippocampus. The hippocampus receives cholinergic innervation mainly from the medial septum-diagonal band complex via the fimbria-fornix. A fine network of cholinergic fibers projects to the hippocampus and dentate gyrus, and synaptic contacts are made onto pyramidal cells, granule cells, interneurons, and neurons of the hilus. In addition to direct synaptic connections, ACh may spill out of synaptic contacts and also produce volume transmission within the hippocampus via non-synaptic signaling^, (MS: medial septum, n Bas: nucleus Basalis, vDB: vertical Diagonal Band, hDB: horizontal Diagonal Band, SI: sublenticular substantia innominata, mHb: medial Habenula, LDT: Laterodorsal Tegmentum, PPT: Pedunculopontine Tegmentum, IPn: Interpeduncular nucleus. Adapted from© 1991, with permission from Elsevier ).

Figure 2

Schematic illustration showing some of the known subcellular regions of nAChR expression. Presynaptic and somatic expression of nAChRs, as well as their specific subunit composition can have important ramifications for how they affect neuronal function and plasticity. The combination of presynaptic facilitation of neurotransmitter release and postsynaptic depolarization and Ca²⁺ influx can enhance or possibly evoke synaptic plasticity (purple shows preterminal expression, light blue is presynaptic, and dark blue is postsynaptic or extrasynaptic. Adapted from© 2004 by Cold Spring Harbor Laboratory Press.

Figure 3

Nicotinic activation can shift STP to LTP within a specific time window. (A) Schematic illustration showing the placement of the stimulating electrode in the Schaffer collateral pathway, the recording electrode on the CA1 pyramidal cell, and the ACh application pipette in the dendrites of the CA1 neuron. For this experiment, stimulation was given at 100 Hz for 1 s and depolarization of the postsynaptic cell was induced by a 100 pA current injection for 1 s. The ACh concentration in the puffer pipette was 1 mmol/L and drug applications were from 0.5–1 s in duration. (B) Recordings of postsynaptic potentials in a CA1 pyramidal cell. This recording shows the LTP that occurs when ACh is puffed 2 s prior to the delivery of the stimulation/depolarization paradigm that normally produces STP. Adapted from © 2005 by the Society for Neuroscience.