Table 2.
Molecular, Anatomical and Functional features of intact striatum, primary fetal striatal grafts, and pluripotent stem cell-derived grafts †.
| Striatal grafts (selected refs) | Notes* | PSC grafts (all refs ††) | |
|---|---|---|---|
| Cell morphology (Golgi): | |||
| MSN : 90–95% medium sized spiny projection | Roberts and DiFiglia (1988), Wictorin et al. (1989), Helm et al. (1990), Clarke et al. (1994), Olsson et al. (1995) | + [in P zones] | ? |
| SIN : 4–8% medium sized spiny and non-spiny | Roberts and DiFiglia (1988), Helm et al. (1990), Clarke et al. (1994) | + [in P zones] | ? |
| GCN : 1–2% giant aspiny neurons | Helm et al. (1990, 1992) | + [in P zones] | ? |
| Astrocytes : structural and reactive | Petit et al. (2002), Zhu et al. (2013) | + [patchy] | + Kallur et al. (2006), Joannides et al. (2007b), Song et al. (2007) |
| Oligodendrocytes : myelinating internal capsule | ? | ? | |
| [Microglia : in response to damage or inflammation] | Freeman et al. (2000) | – [throughout] | ? |
| [pallidal-like, medium, aspiny] | Graybiel et al. (1989), Clarke et al. (1994) | + [in NP zones] | ? |
| [cortical-like, pyramidal—in NP zones] | Clarke et al. (1994) | + [in NP zones] | ? |
| Neurotransmitters: | |||
| MSN and SIN: GABA, GAD | Isacson et al. (1985), Roberts and DiFiglia (1988), Clarke and Dunnett (1993), Piña et al. (1994b) | + | −Nasonkin et al. (2009), Vazey et al. (2010) |
| + Dinsmore et al. (1996), Lee et al. (2006), Song et al. (2007), Arber et al. (in press) | |||
| MSN: Enk, proenkephalin | Roberts and DiFiglia (1988), Graybiel et al. (1989), Sirinathsinghji et al. (1990), Emerich et al. (1991), Campbell and Björklund (1995), Freeman et al. (2000) | + [in P zones] | Ma et al. (2012) |
| MSN: Dyn, prodynorphin | Sirinathsinghji et al. (1990) | + | ? |
| MSN: SP, preprotachykinin | Sirinathsinghji et al. (1990), Helm et al. (1992), Campbell and Björklund (1995), Freeman et al. (2000) | + [in P zones] | Ma et al. (2012) |
| SIN: parvalbumin, PV | Capetian et al. (2009) | + | + Saporta et al. (2001), Kallur et al. (2006), Nasonkin et al. (2009) |
| SIN: calretinin, CR | Freeman et al. (2000), Keene et al. (2007), Capetian et al. (2009) | + [in P zones] | + Saporta et al. (2001), Kallur et al. (2006), Nasonkin et al. (2009), El-Akabawy et al. (2011) |
| SIN: neuropeptide Y, preproNPY | Morris et al. (1989), Sirinathsinghji et al. (1990) | + [in P zones] | ? |
| SIN: somatostatin, SOM | Graybiel et al. (1989), Morris et al. (1989), Freeman et al. (2000), Capetian et al. (2009) | + [in P zones] | ? |
| SIN: nitric oxide synthase, NOS | ? | ? | |
| GCN: Acetylcholine, ChAT, AChE | Graybiel et al. (1989), Helm et al. (1992), Freeman et al. (2000) | + [in P zones] | + Dinsmore et al. (1996), Ma et al. (2012) |
| calbindin, calbindin D28k | Graybiel et al. (1989), Freeman et al. (2000) | + [P and NP zones] | + Saporta et al. (2001), El-Akabawy et al. (2011), Ma et al. (2012), Arber et al. (in press) |
| Molecular markers | |||
| Pluripotent cell markers (Sox1 etc) | ? | ? | |
| Neuronal precursors (TUJ1, Nestin, NSE, DCx etc) | ? | + Dinsmore et al. (1996), Kallur et al. (2006), Lee et al. (2006), Joannides et al. (2007b), Song et al. (2007), Nasonkin et al. (2009), Delli Carri et al. (2013) | |
| zones of tumor/teratoma overgrowth | +/− | + Song et al. (2007), Aubry et al. (2008), Vazey et al. (2010) | |
| MSNs: DARPP-32 | Wictorin et al. (1989), Labandeira-García et al. (1991), Campbell and Björklund (1995), Freeman et al. (2000), Keene et al. (2007) | + [in P zones] | –Vazey et al. (2010), El-Akabawy et al. (2012) + (Kallur et al. (2006), Nasonkin et al. (2009), El-Akabawy et al. (2011), Ma et al. (2012), Delli Carri et al. (2013), Nicoleau et al. (2013), Arber et al. (in press) |
| MSNs: FoxP1, FoxP2, Ctip2 | +/? | + Ma et al. (2012), Delli Carri et al. (2013), Nicoleau et al. (2013), Arber et al. (in press) | |
| SINs: NADPH diaphorase | Roberts and DiFiglia (1988), Emerich et al. (1991), Pundt et al. (1996) | + | ? |
| SINs: NKX2.1, | ? | + Aubry et al. (2008), El-Akabawy et al. (2011) | |
| SINs: Mash1, | ? | + El-Akabawy et al. (2011) | |
| SINs: Dlx1, Dlx2 | ? | + El-Akabawy et al. (2011) | |
| VMAT1 | ? | + Kallur et al. (2006) | |
| Striatal enriched phosphoprotein, STEP | Fricker et al. (1994) | + [in P zones] | |
| Efferent projections | |||
| Direct pathway : MSNs > GPi | Wictorin et al. (1990b) | + | ? |
| Direct pathway : MSNs > SNr | Wictorin et al. (1989, 1990b) | + | Ma et al. (2012) |
| Indirect pathway : MSNs > GPe | Wictorin et al. (1989, 1990b), Clarke and Dunnett (1993), Olsson et al. (1995) | + [from P zones] | Nasonkin et al. (2009) |
| [outgrowth into neocortex] | Wictorin et al. (1990a) | + [aberrant] | |
| Afferent projections | |||
| Neocortex layer III and V, glutamate, topographic | Pritzel et al. (1986), Wictorin and Björklund (1989), Wictorin et al. (1989) | + [P and NP zones] | Ma et al. (2012) |
| Substantia nigra compacta, dopamine (CCK-) | Pritzel et al. (1986), Clarke et al. (1988), Wictorin et al. (1989), Labandeira-García et al. (1991), Clarke and Dunnett (1993), Capetian et al. (2009) | + [into P zones] | Ma et al. (2012), Arber et al. (in press) |
| Raphé nucleus, serotonin | Wictorin et al. (1988), Labandeira-García et al. (1991), Pierret et al. (1998), Petit et al. (2002) | + | ? |
| Thalamus, VA, VL …, glutamate (?) | Pritzel et al. (1986), Wictorin et al. (1988) | + | ? |
| Electrophysiology | |||
| in vitro membrane properties | Walsh et al. (1988), Siviy et al. (1993) | + [normal or aberrant] | ? |
| Local connections > EPSPs | Walsh et al. (1988) | + [EPSPs + IPSPs] | ? |
| Patch-clamp features of inward rectifying current | Surmeier et al. (1992) | + [relatively normal] | ? |
| responses to pharmacological challenges | Nakao et al. (2000), Chen et al. (2002) | + | ? |
| Monosynaptic EPSPs cortex > MSN | Rutherford et al. (1987), Walsh et al. (1988), Xu et al. (1991) | + [aberrant] | ? |
| Monosynaptic EPSPs nigra > MSN | ? | ? | |
| Monosynaptic EPSPs thalamus > MSN | Xu et al. (1991) | + [aberrant] | ? |
| Monosynaptic IPSPs : MSN > GPe | ? | ? | |
| Monosynaptic IPSPs : MSN > GPi | Nakao et al. (1999) | + | ? |
| Monosynaptic IPSPs : MSN > SNr | + [aberrant] | ? | |
| LTP and LTD plasticity at corticostriatal synapse | Mazzocchi-Jones et al. (2009, 2011) | + | ? |
| Fast spiking interneurons | ? | ? | |
| Receptors | |||
| dopamine D1, D2 receptors | Isacson et al. (1987), Deckel et al. (1988b), Liu et al. (1990), Lu and Norman (1993) | + | ? |
| glutamate NMDA receptors | Siviy et al. (1993), Hussain et al. (2004) | + | ± Nasonkin et al. (2009) |
| GABA receptors | ? | ? | |
| ACh muscarinic receptors | Isacson et al. (1987), Deckel et al. (1988a), Liu et al. (1990), Lu and Norman (1993) | + | ? |
| µ-Opiate receptors | Isacson et al. (1987), Lu and Norman (1993) | + [in P zones] | ? |
| cannabinoid CB1 and CB2 receptors | ? | ? | |
| adenosine receptors | ? | ? | |
| CCK receptors | Lu and Norman (1993) | + | ? |
| Neurochemistry | |||
| Striatal derived GABA release in striatum or GP | Sirinathsinghji et al. (1988), Campbell et al. (1993) | + | ? |
| Striatal CCK regulation of DA release | Sirinathsinghji et al. (1993) | + | ? |
| Functional recovery | |||
| Motor—activity and locomotion | Isacson et al. (1984), Deckel et al. (1986) | + | Ma et al. (2012) |
| Motor asymmetry, rotation | Dunnett et al. (1988), Norman et al. (1988, 1989) | + | +Song et al. (2007), Delli Carri et al. (2013) |
| Motor coordination and balance (e.g., rotarod) | Giordano et al. (1990) | + | –El-Akabawy et al. (2012) + Lee et al. (2006), Ma et al. (2012) |
| Motor skills—e.g., paw reaching | Dunnett et al. (1988), Montoya et al. (1990), Döbrössy and Dunnett (2001), Klein et al. (2013) | + | ? |
| Sensorimotor, e.g., neglect | Deckel et al. (1986) | + | ? |
| Motor learning | Mayer et al. (1992), Döbrössy and Dunnett (1998), Brasted et al. (1999) | + | ? |
| Cognition—classic prefrontal tasks, e.g., delayed alternation | Deckel et al. (1986), Dunnett and White (2006) | + | ? |
| Cognition—simple learning tasks, e.g., passive avoidance | Piña et al. (1994a), Giordano et al. (1998) | + | ? |
| Cognition—S-R vs. incentive based learning | ? | ? | |
| Cognition—executive function, e.g., set shifting | ? | ? | |
| Psychiatric—impulsivity and disinhibition | Reading and Dunnett (1995) | + | ? |
| Psychiatric—sensitivity to reward and motivation | ? | ? |
†This table provides a summary of the range of morphological, neurotransmitter, receptor, molecular, cellular, functional features of the normal striatum against which primary fetal and stem cell derived grafts have been evaluated. Comprehensive review is beyond the scope of the present application; see individual references for details.
††See Table 1 for full description.
Abbreviations: CCK, cholecystokinin; CR, calretinin; Dyn, dynorphin; Enk, enkephalin; GABA, gamma-amino butyric acid; GCN, giant cholinergic interneurons; GPe, external segment of globus pallidus; GPi, internal segment of globus pallidus; LTD, long-term depression; LTP, long-term potentiation; MSN, striatal medium spiny projection neurons; NOS, nitric oxide synthase; NPY, neuropeptide Y; PSC, pluripotent stem cell; PV, parvalbumin; SIN, striatal interneuron; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; SOM, somatostatin; SP, substance P; VA, ventral anterior nucleus ; VL, ventrolateral nucleus.
*Notes. + Present. – Absent, ? no known published data.