High-Frequency Afferent Stimulation Induces Long-Term Potentiation of Field Potentials in the Ventral Tegmental Area

Abstract

Excitatory synapses on dopamine neurons in the VTA can undergo both long-term potentiation and depression. Additionally, druginduced plasticity has been found at VTA synapses, and is proposed to play a role in reward-related learning and addiction by modifying dopamine cell firing. LTP at these synapses is difficult to generate experimentally in that it requires an undisturbed intracellular milieu and is often small in magnitude. Here, we demonstrate the induction of LTP as a property of evoked field potentials within the VTA. Excitatory field potentials were recorded extracellularly from VTA neurons in acute horizontal midbrain slices. Using extracellular and intracellular recording techniques, we found that evoked field potentials originate within the VTA itself and are largely composed of AMPA receptor-mediated EPSPs and action potentials triggered by activation of glutamatergic synapses on both dopamine and GABA neurons. High-frequency afferent stimulation (HFS) induced LTP of the field potential. The induction of this LTP was blocked by application of the NMDAR antagonist, d-APV, prior to HFS. As reported previously, glutamatergic synapses on GABA neurons did not express LTP while those on dopamine neurons did. We conclude that the potentiation of glutamatergic synapses on dopamine neurons is a major contributor to NMDA receptor-dependent LTP of the field potential. Field potential recordings may provide a convenient approach to explore the basic electrophysiological properties of VTA neurons and the development of addiction-related processes in this brain region.

PKG and PKA Signaling in LTP at GABAergic Synapses

“…As we previously reported (Nugent et al , 2007; Nugent et al , 2008), GABAergic synapses on VTA DA neurons undergo LTP in response to patterned local electrical stimulation (LTP GABA , Figure 1a). LTP GABA appears to be expressed by an increase in presynaptically released GABA, as the paired pulse ratio and coefficient of variation change after induction (Nugent et al , 2007).…”

Peroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors

“…To ensure that PPARα modulation of DA neuronal firing was not restricted to a certain DA subpopulation within the VTA, the effects of both MK886 and WY14643 were also investigated using extracellular evoked field potential recordings in horizontal brain slices (23). Figure 6 (A) shows that MK886 (500 nM, 5 min) induced a significant change in both negative components of the field potential (i.e.…”

“…Recordings were made from horizontal slices superfused with artificial cerebrospinal fluid (ACSF, 37° C) saturated with 95% O 2 and 5% CO 2 containing (in mM): 126 NaCl, 1.6 KCl, 1.2 NaH 2 PO 4 , 1.2 MgCl 2 , 2.4 CaCl 2 , 18 NaHCO 3 , and 11 glucose. Evoked field potential recordings were as described previously (23) and Supplement 1.…”

Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

“…Subsequently, LTP has been investigated in a variety of mammalian species utilizing in vitro approaches including rat (Douglas and Goddard, 1975), mouse (Nosten-Bertrand et al, 1996), guinea pig (Harris and Cotman, 1986), monkey (Urban et al, 1996), and human (Chen et al, 1996; Beck et al, 2000; Cordoba-Montoya et al, 2010). Since its initial demonstration in the hippocampus (Bliss and Gardner-Medwin, 1973; Bliss and Lomo, 1973; Douglas and Goddard, 1975), LTP has been observed in various brain regions throughout the mammalian CNS, including the amygdala (Clugnet and LeDoux, 1990; Rogan et al, 1997; Sigurdsson et al, 2007), cortex (Artola and Singer, 1987; Teyler, 1989; Jung et al, 1990; Tsumoto, 1990; Kirkwood et al, 1993; Fox, 2002), striatum (Calabresi et al, 1992; Charpier and Deniau, 1997; Lovinger, 2010), ventral tegmental area (Nugent et al, 2007, 2008), cerebellum (Salin et al, 1996; Lev-Ram et al, 2002), and nucleus accumbens (Pennartz et al, 1993; Kombian and Malenka, 1994; Schotanus and Chergui, 2008). LTP can be observed both in vitro as well as in vivo condition.…”