Cocaine Experience Enhances Thalamo-Accumbens N-Methyl-D-Aspartate Receptor Function

Abstract

BACKGROUND Excitatory synaptic transmission in the nucleus accumbens (NAc) is a key biological substrate underlying behavioral responses to psychostimulants and susceptibility to relapse. Recent studies have demonstrated that cocaine induces changes in glutamatergic signaling at distinct inputs to the NAc. However, consequences of cocaine experience on synaptic transmission from the midline nuclei of the thalamus (mThal) to the NAc have yet to be reported. METHODS To examine synapses from specific NAc core inputs, we recorded light-evoked excitatory postsynaptic currents (EPSCs) following viral-mediated expression of channelrhodopsin-2 in the mThal, prefrontal cortex (PFC), or basolateral amygdala (BLA) from acute brain slices. To identify NAc medium spiny neuron (MSN) subtypes we utilized mice expressing tdTomato driven by the promoter for the dopamine receptor subtype 1 (D1). We recorded N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) properties to evaluate synaptic adaptations induced by cocaine experience, a 5-day cocaine exposure followed by 2-weeks of abstinence. RESULTS We determine that excitatory inputs to the NAc core display differential NMDAR properties and cocaine experience uniquely alters AMPAR and NMDAR properties at mThal-D1(+), mThal-D1(−), and PFC-D1(+) synapses, but not PFC-D1(−) synapses. Finally, at mThal-D1(+) synapses, we demonstrate that cocaine enhances GluN2C/D function and NMDAR-dependent synaptic plasticity. CONCLUSIONS Our results identify contrasting cocaine-induced AMPAR and NMDAR modifications at mThal- and PFC-NAc core synapses. These changes include an enhancement of NMDAR function and plasticity at mThal-D1(+) synapses. Incorporation of GluN2C/D-containing NMDARs most likely underlies these phenomena and represents a potential therapeutic target for psychostimulant use disorders.

Feasibility study for the measurement of πN transition distribution amplitudes at P¯Singh1, Erni2, Krusche3 et al. 2017Phys. Rev. D401250View full textAdd to dashboardCite

“…Figure 5 shows the Δ 2 T dependence of the cross section for the three collision energies which are used for the studies addressed here, each of them limited to its validity range. It is possible to compare this prediction to the E835 measurement of thepp → J=ψπ 0 → e þ e − π 0 cross section [17][18][19], taken at an incidentp momentum of 5.5 GeV=c that corresponds to s ¼ 12.3 GeV 2 or ffiffi ffi s p ¼ 3.5 GeV. This value of ffiffi ffi s p is 25 MeV below the threshold for the production of the h c resonance.…”

“…energy s: 12.3 GeV 2 , 16.9 GeV 2 , and 24.3 GeV 2 . The first value is chosen to coincide with existing data from E835 forpp → J=ψπ 0 [17][18][19]. The remaining two values are chosen at the incidentp momenta of 8 GeV=c and 12 GeV=c, respectively, to explore the kinematic zone between the first point and the maximum availablep momentum at FAIR of 15 GeV=c.…”

“…The simultaneous measurement of both resonant and nonresonant channels provides constraints to the πN TDAs in different kinematic ranges and allows one to test the universality of πN TDAs. While the nonresonantpp → γ Ã π 0 → e þ e − π 0 has never been measured, some scarce data exist forpp → J=ψπ 0 → e þ e − π 0 [17][18][19], which can be used to constrain the predictions. Production of a J=ψ with an associated π 0 inpp collisions has indeed been investigated in the past by the E760 experiment at FNAL, since it constitutes a background in the search for charmonium states via their decay into J=ψπ 0 .…”

N-Methyl-D-Aspartate Receptors: “C”ing the Culprits Behind Cocaine-Induced Metaplasticity

“…In this issue of Biological Psychiatry , Joffe and Grueter (5) provide significant insight into these critical questions. Using projection-specific optogenetic approaches in a transgenic mouse line with genetically labeled D 1 MSNs, they identified differential adaptations in synaptic AMPARs and NMDARs within several key excitatory projections to NAc D 1 and D 2 MSNs after cocaine withdrawal.…”

“…Among several projections to the NAc, Joffe and Grueter (5) singled out the midline thalamic (mThal) input to D 1 -positive and D 1 -negative (putative D 2 -expressing) MSNs within the NAc core. To do so, they recorded excitatory postsynaptic currents (EPSCs) in D 1 and D 2 MSNs evoked by optogenetic stimulation of mThal afferents in the NAc core from mice withdrawn from cocaine.…”