Fig. 2.

Newly generated medium spiny neurons integrate into the 2 major output pathways of the basal ganglia. (A) Schematic representation of the different neural pathways of the basal ganglia and related structures. The red arrow indicates Substance P-expressing medium spiny neurons of the direct pathway. The green arrow indicates Enkephalinergic medium spiny neurons of the indirect pathway. Following intraventricular injection of adeno-associated virus serotype 4 (AAV-4)-brain-derived neurotrophic factor/Noggin, the newly generated medium spiny neurons in the rat striatum expressed either Substance P (B) or Enkephalin (Enk.) (C) neurotransmitters. Thus, these neurons integrate as part of the direct or indirect pathway as shown in the schematic. (D) Intrapallidal injection of fluorescent microspheres (FMS), a retrograde tracer, allowed identification of newly generated neurons that successfully extended axonal fibers to the globus pallidus, the natural target of medium spiny neurons. BrdU = 5-bromo-2'-deoxyuridine; Enk = enkephalin; GPe = globus pallidus externalis; GPi = globus pallidus internalis; SNpc = substantia nigra pars compacta; SNpr = substantia nigra pars reticulata; S-P = substance P; StN = subthalamic nucleus; Th = Thalamus. Scale bar = 10 μm