Spiny projection neuron

Spiny projection neurons all contain glutamic acid decarboxylase (GAD) the synthetic enzyme for the neurotransmitter GABA (Kita and Kitai 1988). In addition, most of those neurons projecting to the globus pallidus alone contain the neuropeptide enkephalin, whereas most of those which project to the substantia nigra contain the neuropeptides substance P and dynorphin (Beckstead and Kersey 1985 Gerfen and Young 1988 Haber and Watson 1983). Spiny projection neurons contain different complements of neurotransmitter receptors, and other proteins that serve to characterize particular subpopulations of striatal output neurons. These will be discussed in further detail below. 

Spiny projection neurons receive inputs from the cortex, thalamus and amygdala, which make asymmetric synapses on dendritic spines, and to a lesser degree, dendritic shafts. These inputs provide the major excitatory input to these neurons. In addition, a number of inputs from outside the striatum, and from within the striatum provide inputs that function to modify the responsiveness of spiny neurons to the excitatory input. These include inputs from dopamine afferents from the substantia nigra, inhibitory GABA inputs from the axon collaterals of other spiny neurons, inhibitory inputs from GABA (and peptide containing) striatal interneurons, and inputs from cholinergic striatal interneurons. 

Consistent with the asymmetric character of corticostriatal synapses onto spiny neurons electrophysiologic studies have demonstrated that corticostriatal input evokes a monosynaptic excitatory post-synaptic potential (EPSP) (Kitai et al. 1976 Wilson 1986). At least two types of corticostriatal afferents have been identified, on the basis of the electrophysiologic effects of these inputs (Jinnai and Matsuda 1979 Wilson 1986). One is a fast conducting collateral of neurons projecting to the brainstem and evokes an EPSP with a latency of 3 msec. A second type, which appears to be the major corticostriatal afferent, is a slower conducting afferent that evokes an EPSP with a latency of 10 msec. 

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The NAc is the major component of the ventral striatum, and of the so-called limbic striatum. This striatal region corresponds to the entire anterior and ventromedial sector of the striatum and continues anteriorly into the NAc and the olfactory tubercle (Heimer and Wilson, 1975 Nauta, 1989). In the NAc, the principal neurons, which are the medium spiny projection neurons, make up approximately 90% of the total neuronal population and are generally similar to those of the striatal (i.e., neostriatal) counterpart. The local circuit neurons represent approximately 10% of the NAc neurons and vary greatly in size,... 

The immediate and reversible actions of dopamine are a combination of modulations of individual ion channels. The major ion channels expressed in spiny projection neurons are summarized in Table 2. Current understanding of the properties of these channels is mostly based on whole cell recordings from isolated cells, which have been recently reviewed by Nichola et al. (2000). The role of these channels in whole cell behavior has been studied using intracellular recordings in brain slices or anaesthetized animals. Many of the important cellular properties of spiny projection neurons can be accounted for in terms of ion channel activations occurring at different membrane potentials. 

TABLE 2. Electrophysiologically characterized currents in spiny projection neurons Electrophysiologically-defined current References... 

Slow and persistent Na+ channels represented by INa are responsible for regenerative events underlying subthreshold ramp depolarizations and action potential firing in spiny projection neurons. This current normally produces a depolarizing prepotential, just before the action potential. The prepotential is sensitive to the sodium-channel blocker, TTX but not to calcium channel blockers (Bargas et al., 1989). It is responsible for the... 

Modulatory effects may be postsynaptically mediated by interactions within the spiny projection neurons, or involve presynaptic regulation of neurotransmitter release from corticostriatal terminals. Postsynaptic effects may be mediated by direct actions of intracellular signaling pathways (cAMP, calcineurin) on receptor status (phosphorylation/ dephosphorylation of receptor proteins), and actions on voltage-dependent channels, which may amplify or attenuate the electrical response of the cell to synaptic currents. 

In the light of our data showing LTP to be dopamine-dependent, it seems likely that the facilitation of LTP in Mg-free conditions may be brought about by increased HFS-induced release of dopamine. Increased dopamine release occurs in Mg++-free solution due to activation of presynaptic NMDA receptors, presumably located on dopaminergic nerve terminals (Roberts and Sharif, 1978 Krebs et al., 1991a,b Desce et al., 1992). As noted above, the dopaminergic terminals on spiny projection neurons synapse in close... 

Galarraga E, Pacheco-Cano MT, Flores-Hernandez JV, Bargas J (1994) Subthreshold rectification in neostriatal spiny projection neurons. Exp Brain Res 100 239-249. 

Nisenbaum ES, Xu ZC, Wilson CJ (1994) Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons. J Neurophysiol 77 1174-1189. 

Nisenbaum ES, Wilson CJ (1995a) Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons. J Neurosci 75 4449-4463. 

Nisenbaum ES, Wilson CJ (1995b) The role of potassium currents in the subthreshold responses of neostriatal spiny projection neurons. In Ariano MA, Surmeier DJ (Eds), Molecular and Cellular Mechanisms of Neostriatal Function, pp. 165-181. R.G. Landes Company, Austin. 

Fig. 3. View of a single striatal spiny projection neuron, intracellularly filled with biocytin, in a sagittal section of the striatum (A) and at higher magnification (B). Corticofugal fiber fascicles are clearly evident coursing through the striatum. Spiny projection neurons are labeled within the striatum with calbindin iramunoreactiv-...

Fig. 6. A-C. Three examples of intracellularly filled striatal spiny projection neurons. Dendrites, shown in black, are densely laden with spines and extend in an area approximately 200-300 /rm around the cell body. Local axon collaterals of these neurons, depicted in gray, spread in area approximately 200 00 /um around the cell body, which does not precisely overlap the dendritic spread of these neurons. Adapted from Kawaguchi et al. 1990.

Fig. 9. Summary of the major synaptic inputs to spiny projection neurons. Inputs to the cell bod> arise mainly from striatal intemeurons. Inputs to proximal dendrites are mainly from striatal interneurons and other spiny projection neurons. Inputs to distal dendrites arise from extrastriatal sources, from the cortex (asymmetric/ glutamatergic) to the spine heads, from dopamine neurons in the midbrain (symmetric/dopamine) to the necks of spines and to interspine shafts. Other spiny projection neurons also provide symmetric inputs to the necks of spines and to interspine shafts.

Fig. 13. A) Diagram showing an example of inputs to the globus pallidus (GP) from striatal spiny projection neurons. Typically there are two major sites of axonal arborization, one in the region immediately adjacent to the striatum and a second in the central region of the GP. B) Stylized drawing of two pallidal neurons showing how the dendrites of neurons are confined within the two regions of the GP that conform to the pattern of striatal inputs. C) The axonal projection of a globus pallidus neuron of the type with discoid dendrites, which provides collaterals to the striatum (CP), to the entopeduncular nucleus (EP), subthalamic nucleus (stn) and substantia nigra (SN). Adapted from Kita and Kitai 1994.

Fig. 24. Patch and matrix striatal compartments are labeled with neurochemical markers. A) The patch compartment is labeled with 3H-naloxone binding to mu opiate receptors (white in the darkfield photomicrograph). B) The matrix compartment is labeled with calbindin-immunoreactivity, which labels spiny projection neurons that provide inputs to the substantia nigra pars reticulata. The correspondence between calbindin-poor zones (black arrows) and mu opiate binding sites (white arrows) is seen to occur in all regions of the striatum. Calbindin-immunoreactivity is relatively weak in the dorso-lateral striatum, which nonetheless contains opiate receptor patches.

Fig. 29. Coronal sections through the striatum showing mu-opiate receptor with 3H-naloxone binding of patches (A and B) and in adjacent sections spiny projection neurons labeled by in situ hybridization histochemistry with probes directed against substance P mRNA (A ) and enkephalin mRNA (B ). Substance P and enkephalin are expressed by different populations of spiny projection neurons, each comprising about half of the population and each evenly distributed in both patch and matrix compartments (arrows show patches in the corresponding sections). From Gerfen and Young (1987).

Penney GR, Wilson CJ, Kitai ST (1988) Relationship of the axonal and dendritic geometry of spiny projection neurons to the compartmental organization of the neostriatum. J. Comp. Neurol., 269, 275-289. 

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