Corticostriatal Paired-Pulse Potentiation Produced by Voltage-Dependent Activation of NMDA Receptors and L-Type Ca²⁺ Channels

Abstract

AMPA and N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses expressed differential paired-pulse plasticity when examined in the same cell using intracellular or whole cell voltage-clamp recordings. Electrical stimulation of corticostriatal afferents in brain slices bathed in artificial cerebrospinal fluid containing bicuculline produces excitatory postsynaptic potentials and excitatory postsynaptic currents (EPSCs) mediated primarily by AMPA receptors. Cell-to-cell variation existed in AMPA receptor paired-pulse plasticity, but within-cell plasticity was stable over a range of stimulation intensities. Addition of 6-cyano-7-nitroquinoxalene-2,3-dione blocked most of the synaptic response leaving behind a small AP-5-sensitive component. Increasing the stimulation intensity produced large, long-lasting NMDA receptor-mediated responses. In contrast to AMPA receptor-mediated responses, NMDA receptor responses consistently showed an increase in paired-pulse potentiation with increasing stimulation intensity. This relationship was restricted to interstimulus intervals shorter than 100 ms. Paired-pulse potentiation of NMDA receptor responses was voltage-dependent and reduced by removal of extracellular Mg(2+). Block of postsynaptic L-type Ca(2+) channels with nifedipine produced a voltage-dependent reduction of NMDA receptor excitatory postsynaptic currents (EPSCs) and a voltage-dependent reduction of NMDA receptor paired-pulse potentiation. These data indicate depolarization during the first NMDA receptor response causes facilitation of the second by removing voltage-dependent block of NMDA receptors by Mg(2+) and by activating voltage-dependent Ca(2+) channels.

Dopamine Modulates Release from Corticostriatal Terminals

“…It may be that subpopulations of corticostriatal terminals express different receptors, as suggested by electrophysiological (Flores-Hernandez et al, 1997;Akopian and Walsh, 2002;Bamford et al, 2004) or ultrastructural immunocytochemical studies (Wang and Pickel, 2002). Corticostriatal terminals in control mice appear to be segregated into two groups based on their response to dopamine, with slower destaining terminals (ϳ85%) responding to dopamine by an additional reduction in activity.…”

“…1 A) is composed of medium spiny neurons (MSNs) that receive excitatory corticostriatal glutamatergic projections, forming asymmetric synaptic contacts on distal dendrites (Dube et al, 1988;Smith et al, 1994;Wilson, 1995), and dopaminergic nigrostriatal fibers that form symmetrical synapses on the necks of dendritic spines (Pickel et al, 1981). Although this anatomical configuration suggests that dopamine has a direct modulatory effect on cortical signaling (Arbuthnott et al, 1998), the role of dopamine in presynaptic modification of corticostriatal afferents has been controversial because of the extraordinary complexity of MSN innervation (Akopian and Walsh, 2002) and the challenges inherent in using postsynaptic recordings to determine alterations in presynaptic activity (Van der Kloot, 1991;Sulzer and Pothos, 2000). Electron microscopy (Fisher et al, 1994;Sesack et al, 1994;Wang and Pickel, 2002) and electrophysiology (Calabresi et al, 1993;O'Donnell and Grace, 1994;Hsu et al, 1995;Flores-Hernandez et al, 1997;Cepeda et al, 2001;Tang et al, 2001;Bamford et al, 2004) studies, however, have supported the concept that dopamine directly regulates glutamate release from corticostriatal terminals by stimulating D2 receptors located on a subpopulation of cortical afferents, providing a mechanism for dampening critical cortical signals (Bamford et al, 2004).…”

Encoding and Decoding Bursts by NMDA Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons

“…The best studied mechanisms mediating STP are presynaptic, most notably changes in release probability (Zucker and Regehr, 2002). Postsynaptic dendritic mechanisms can have different effects on STP; in some cases, they increase short-term facilitation (Akopian and Walsh, 2002) and in others, they reduce summation of high-frequency synaptic inputs, making synaptic signaling more linear (Magee, 1998). In this work, we have described a form of STP in basal dendrites involving the facilitation of the total postsynaptic NMDA conductance during repeated synaptic activation.…”

“…First, whereas the dynamics of classical STP are determined solely by the history of the specific activated synapse (but see Akopian and Walsh, 2002 for a discussion of cooperative potentiation), the degree of amplification during burst activation of NMDA receptors depends on the intensity of postsynaptic activation, changing abruptly at the transition between inputs that are subthreshold versus suprathreshold for NMDA spike initiation. Second, the degree of amplification by NMDA channels also depends on the history of activation of neighboring synapses, because NMDA spike initiation will in general depend on the coactivation of numerous synapses located within the same dendritic compartment (Polsky et al, 2004).…”

Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

“…In the current study, EPSPs were mediated by AMPA/ kainate receptor channels with negligible contribution of NMDA receptor channels (Fig. 1C) (n ϭ 3) and had a single rising phase with a rise time (2.30 Ϯ 0.09 ms; n ϭ 116), latency (2.75 Ϯ 0.08 ms; n ϭ 116), and half-width (16.9 Ϯ 0.6 ms; n ϭ 116) (supplemental Table 1, available at www.jneurosci.org as supplemental material) as described previously (Kawaguchi et al, 1989;Jiang and North, 1991;Walsh and Dunia, 1993;Kita, 1996;Akopian and Walsh, 2002). Together, this shows that only SPNs and evoked monosynaptic corticostriatal EPSPs were included in the present study.…”