Nicotine Induces Glutamate Release from Thalamocortical Terminals in Prefrontal Cortex

Abstract

It has been proposed that activation of nicotinic acetylcholine receptors (nAChRs) can activate the prefrontal cortex, enhancing attention and cognition. Nicotine can stimulate the release of several different neurotransmitters in many brain regions. In the present study, we found that stimulation of nAChRs by nicotine or the endogenous agonist, acetylcholine (ACh), induces a large spontaneous increase in glutamate release onto layer V pyramidal neurons of the prefrontal cortex. This release of glutamate, measured by spontaneous excitatory postsynaptic currents (sEPSCs) in the prefrontal cortical slice, depends on intact thalamocortical terminals. It can be suppressed by m-opioids or eliminated by blocking action potentials. The increase in sEPSCs is sensitive to low concentrations of nicotine, suggesting the involvement of high-affinity (eg a 4 b 2 ) nAChRs. Recent work has shown alterations in prefrontal a 4 b 2 nAChRs in autism and schizophrenia, two conditions that are distinguished by abnormal prefrontal cortical activation as well as difficulty in certain aspects of cognition and integrating social and emotional cues. We show that mice lacking the b 2 nAChR subunit do not show increased sEPSCs with either nicotine or ACh, again implicating high-affinity nicotinic receptors. These findings give new insight into the mechanism by which nicotine affects excitatory neurotransmission to the output neurons of the cerebral cortex in a pathway that is critical for cognitive function and reward expectation.

Chronic Nicotine Alters Nicotinic Receptor-induced Presynaptic Ca2+ Responses in Isolated Nerve Terminals

“…Increased presynaptic [Ca 2+ ]i likely underlies the nicotine-evoked release of neurotransmitter from cortical synaptosomes described previously to involve predominantly α7 nAChRs whose activation, in turn, triggers the opening of N-and P/Q-type VGCCs [25,26], though β2 nAChRs are likely involved as well [27,28]. In addition, increased presynaptic [Ca 2+ ]i also likely underlies nicotine enhancement of neurotransmitter release measured in cortical slices [29][30][31][32][33] and the intact cortex using microdialysis [19,34,35].…”

Functional brain imaging of tobacco use and dependence

“…For example, in response to nicotine, glutamate release has been demonstrated in the prelimbic prefrontal cortex (Gioanni et al, 1999), and glutamate and aspartate release have been demonstrated in the VTA (Schilstrom et al, 2000). The finding of nAChR-induced glutamate release in the prefrontal cortex has also been demonstrated by measuring spontaneous excitatory postsynaptic currents (Lambe et al, 2003). Importantly, one of these studies (Gioanni et al, 1999) also demonstrated that nicotine administration facilitates thalamo-cortical neurotransmission through stimulation of nAChRs on glutamatergic neurons.…”

Nicotine consumption and schizotypy in first-degree relatives of individuals with schizophrenia and non-psychiatric controls

“…The influence of nicotine on these symptoms has been greatly researched. Nicotine actively influences the increase in transmission of particular neurotransmitters in the brain (Avila et al, 2003;Gray et al, 1994;Jacobsen et al, 2004;Kumari and Postma, 2005;Lambe et al, 2003;Larrison-Faucher et al, 2004;Myers et al, 2004;Sacco et al, 2004;Sherr et al, 2002) and the reinforcing effects of nicotine are believed to result from its interaction with the mesocorticolimbic system. Others have suggested that nicotine enhances performance on cognitive tasks through an increase of the synaptic transmission of glutamate (Gray et al, 1996).…”