Characterization of a Nicotine-Sensitive Neuronal Population in Rat Entorhinal Cortex

Abstract

The entorhinal cortex (EC) is a part of the hippocampal complex that is essential to learning and memory, and nicotine affects memory by activating nicotinic acetylcholine receptors (nAChRs) in the hippocampal complex. However, it is not clear what types of neurons in the EC are sensitive to nicotine and whether they play a role in nicotine-induced memory functions. Here, we have used voltage-sensitive dye imaging methods to locate the neuronal populations responsive to nicotine in entorhino-hippocampal slices and to clarify which nAChR subtypes are involved. In combination with patch-clamp methods, we found that a concentration of nicotine comparable to exposure during smoking depolarized neurons in layer VI of the EC (ECVI) by acting through the non-␣7 subtype of nAChRs. Neurons in the subiculum (Sb; close to the deep EC layers) also contain nicotine-sensitive neurons, and it is known that Sb neurons project to the ECVI. When we recorded evoked EPSCs (eEPSCs) from ECVI neurons while stimulating the Sb near the CA1 region, a low dose of nicotine not only enhanced synaptic transmission (by increasing eEPSC amplitude) but also enhanced plasticity by converting tetanus stimulationinduced short-term potentiation to long-term potentiation; nicotine enhanced synaptic transmission and plasticity of ECVI synapses by acting on both the ␣7 and non-␣7 subtypes of nAChRs. Our data suggest that ECVI neurons are important regulators of hippocampal function and plasticity during smoking.

α4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex

“…Previous studies have shown that micro-injection or bath application of nicotine can increase the excitability of corticothalamic (Kassam et al, 2008), entorhinal (Tu et al, 2009) and prefrontal cortical neurons (Vidal and Changeux, 1993;Lambe et al, 2003). However as noted previously, nicotine can also depolarize inhibitory cortical neurons (Couey et al, 2007).…”

Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the Hippocampus and Enhances Cognition

“…Horizontal hippocampal slices (310 m thick) from Wistar rats aged 14 to 18 days were cut with a vibratome in icy artificial cerebrospinal fluid (ACSF) containing 122 mM NaCl, 3.5 mM KCl, 1.3 mM MgCl 2 , 2 mM CaCl 2 , 1.2 mM NaH 2 PO 4 , 25 mM NaHCO 3 , and 10 mM glucose that was continuously bubbled with carboxygen (95% O 2 /5% CO 2 ) [see Tu et al (2009)]. Slices were recovered in the continuously carboxygenated ACSF at room temperature for 1 h before use.…”

Possible contributions of a novel form of synaptic plasticity inAplysiato reward, memory, and their dysfunctions in mammalian brain

“…The D1 receptors involved in LTP have often been thought to be postsynaptic, but they might also be presynaptic. Similarly, activation of nACh receptors in hippocampus and EC produces an increase in spontaneous release of glutamate (Radcliffe and Dani 1998;Radcliffe et al 1999;Liu et al 2003;Sharma and Vijayaraghavan 2003) and activity-dependent LTP (Welsby et al 2006(Welsby et al , 2007Kenney and Gould 2008;Lagostena et al 2008;Tu et al 2009;Gu and Yakel 2011;Gu et al 2012), and blocking nAChRs reduces LTP (Yun et al 2005). Thus presynaptic nACh receptors and spontaneous release might also contribute to LTP in those areas.…”

“…Presynaptic receptors and spontaneous release may play important roles in these effects as well. Thus, activation of presynaptic nACh receptors enhances spontaneous release of glutamate from layer VI to layer V neurons in EC (Tu et al 2009). As in Aplysia, the glutamate could act through group I mGlu receptors to increase postsynaptic Ca 2+ and, in (Fig.…”

“…Results in NAc are mixed, and in some cases presynaptic D1 receptors instead decrease glutamatergic transmission (Nicola and Malenka 1998). Although nicotinic and D1 receptors act through very different molecular mechanisms (see the section on "Synapse-specific effects"), activation of presynaptic nicotinic receptors has the same functional outcome of enhancing spontaneous release of glutamate in hippocampus, EC, PFC, VTA, and other areas (Radcliffe and Dani 1998;Radcliffe et al 1999;Mansvelder and McGehee 2000;Sharma and Vijayaraghavan 2003;Wang et al 2006;Tu et al 2009;Garduño et al 2012). In many of these studies spontaneous release was used as an indicator of presynaptic or postsynaptic changes, but it could also recruit those changes as it does in Aplysia.…”