Nicotinic and Muscarinic Reduction of Unitary Excitatory Postsynaptic Potentials in Sensory Cortex; Dual Intracellular Recording in Vitro Slice Preparation and Recording

muscarinic reduction of unitary excitatory postsynaptic potentials in sensory cortex: dual intracellular recording in vitro. We studied the cholinergic modulation of glutamatergic transmission between neighboring layer 5 regular-spiking pyramidal neurons in somatosensory cortical slices from young rats (P10-P26). Brief bath application of 5–10 ␮M carbachol, a nonspecific cholinergic agonist, decreased the amplitude of evoked unitary excitatory postsynaptic potentials (EPSPs). This effect was blocked by 1 ␮M atropine, a muscarinic receptor antagonist. Nicotine (10 ␮M), in contrast to carbachol, reduced EPSPs in nominally magnesium-free solution but not in the presence of 1 mM Mg ϩ2 , indicating the involvement of NMDA receptors. Likewise, when the postsynaptic cell was depolarized under voltage clamp to allow NMDA receptor activation in the presence of 1 mM Mg ϩ2 , synaptic currents were reduced by nicotine. Nicotinic EPSP reduction was prevented by the NMDA receptor antagonist D-AP5 (50 ␮M) and by the nicotinic receptor antagonist mecamylamine (10 ␮M). Both carbachol and nicotine reduced short-term depression of EPSPs evoked by 10 Hz stimulation, indicating that EPSP reduction happens via reduction of presynaptic glutamate release. In the case of nicotine, several possible mechanisms for NMDAR-dependent EPSP reduction are discussed. As a result of NMDA receptor dependence, nicotinic EPSP reduction may serve to reduce the local spread of cortical excitation during heightened sensory activity. Cholinergic input from the basal forebrain influences corti-cal functions such as learning, memory, and attention (Descar-ries et al. 2004) through the activity of nicotinic and muscarinic receptors. Much of the effect of acetylcholine (ACh) may arise from modulation of excitatory (glutamatergic) synaptic trans-consequent 'gating' of sensory information during arousal (Steriade et al. 2001). Past in vitro studies have used whole cell recording in conjunction with extracellular stimulation in slice preparations to examine cholinergic modulation of cortical excitatory pathways. The general consensus among these studies is that ACh enhances glutamate release at thalamo-cortical synapses via nicotinic receptors while reducing glutamate release at cortico-cortical synapses via muscarinic receptors, at least within superficial, presumably thalamo-recipient layers Acetylcholine's selective enhancement of sensory responses relative to cortico-cortical responses has been corroborated in vivo using natural stimuli (Oldford and Castro-Alamancos 2003). In addition to synaptic effects, ACh and cholinergic agonists change the excitability and firing properties of cortical pyra-midal neurons, primarily through the activity of muscarinic receptors (Krnjevic et al. 1971; McCormick 1992). Moreover, ACh acts on inhibitory neurons as well, both through synaptic effects on GABA release (Metherate and …