Cortical stimulation evokes monosynaptic excitation of THINs and SABIs. In addition, this stimulation evokes disynaptic inhibitory responses only in THINs, probably through the activation of an as yet unidentified GABAergic interneuron or SPNs. Similarly, thalamic stimulation of the PfN evokes monosynaptic excitation of THINs and SABIs. In this case, the excitatory response is accompanied by inhibitory polysynaptic responses in both THINs and SABIs.

EEDQ augments the cocaine-induced locomotor activity of preweanling rats, while attenuating the locomotion of adolescent and adult rats. In the present study, we used NPA-stimulated GTPγS receptor binding, and GRK6 and ARRB2 expressions to test the hypothesis that D2 receptor supersensitivity is responsible for this age-dependent effect.

Small changes in striatal glutamate and dopamine establish goal-directed behaviors, while large changes underlie many neuropsychological disorders. We identify long-lasting but reversible changes along the corticoaccumbal pathway that occur following repeated amphetamine. This synaptic plasticity corresponds with behaviors in mice and may encode motor learning, habit formation, and dependence.

Nucleus accumbens D1-MSN vs. D2-MSN dendrites display differential mitochondrial lengths, with smaller mitochondria occurring in D2-MSN dendrites. This differential size in mitochondria is potentially mediated through the mitochondrial fusion molecules, Opa1, which is differentially enriched in these two neuron subtypes.

Experimental models of Huntington's disease (HD), a genetic neurodegenerative condition characterized by abnormal dopamine (DA)–glutamate interactions and hyperkinesia, show alterations in synaptic plasticity in multiple brain areas. Using an in vitro patch-clamp and intracellular recordings of corticostriatal slices from R6/1 mice, we tested the hypothesis that corticostriatal long-term depression (LTD), a well-conserved synaptic scaling down response to environmental stimuli, is altered in striatal spiny projection neurons (SPNs) of symptomatic R6/1 mice, a HD model with gradual development of symptoms. Our results show that, similar to other models characterized by hyperkinesia and striatal DA receptor pathway dysregulations, both synaptic depotentiation and activity-dependent LTD are impaired in SPNs of mutant mice. Bath application of DA induced an abnormal response of D1 receptors that caused a shift in synaptic plasticity direction resulting in an N-Methyl-d-Aspartate (NMDA)-dependent LTP, in an experimental condition in which NMDA receptors are not recruited in wild-type mice, confirming the role of aberrant DA–glutamate interactions in the defective synaptic scaling down responses associated with HD symptoms.

NT-4/5 antagonizes the effect of BDNF on corticostriatal transmission, while BDNF exhibits a synergic action on the NT-4/5 amplitude increase of the synaptic spike in slices from a toxic model of HD in male mice. The antagonistic or synergistic effect depends on the activation of the TrkB-T1 or TrkB-FL respectively.

Oligomeric forms of α-synuclein are believed to cause neurotoxicity in Parkinson's disease (PD) in part by causing mitochondrial injury. The dopamine metabolite, 3,4-dihydroxyphenyl-acetaldehyde (DOPAL), oligomerized α-synuclein (DOS), which inhibited (−) brain mitochondrial functions including oxygen consumption rate (OCR) and membrane potential. Four unrelated small molecules rescued (+) DOS-induced mitochondrial inhibition.

TH+/dopamine cell counts of the SNpc showed a 36% decrease (p = 0.0036) and a 38% decrease (p = 0.0021) in both the MPTP and SD+MPTP groups compared to the VEH and SD groups, respectively. Photos of TH− labeled SNpc from each treatment group are shown above the graph at 5× and 20× magnification (black arrows point to TH-ir SNpc neurons and red arrows point to Cresyl Violet SNpc neurons).