Table of Contents

SNc: Substantia Nigra, pars compacta (area A9)

Image and Location

NOTE: The SNc and the Ventral Tegmental Area(VTA; area A10) share many functional and anatomical features and are often treated as a single entity. However, there are also important differences, primarily in terms of afferent and efferent connectivity. Also, some DA cells also “spill over” into the adjacent Substantia Nigra, pars reticulata (SNr) proper, but can be considered as belonging to the SNc.

Region of Interest images (ROI):

(Thank you to Jessica! =) )

ROI saggital,coronal


Neurosynth connectivity image:

T. Hazy doesn't know how to do. :-(


Neurosynth structure image:

T. Hazy doesn't know how to do. :-(


avg152_sn.nii.zip This ROI covers the entire SN, as there isn't really sufficient resolution to distinguish SNc/SNr. Drawn on the MNI 152 proton density template. Based on anatomy from this paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076524/ (-Jessica)

Searches

Searches so far:

fMRI [all] and RVM [all]

T. Hazy doesn't know how to do. :-(

Most important references

(classic papers, best papers)

HazyFrankOReilly10

GeislerWise08

JoelWeiner00

BrischouxChakrabortyBrierleyEtAl09

COMMENT: RVM Endnote Package Library (with PDFs)

T. Hazy doesn't know how to do. :-(

Structure

The VTA and Substantia Nigra, pars compacta (SNc; area A9) are generally considered to be the sole source of dopamine (DA) in the brain, except for the oft-neglected retrorubral area (area A8) which is associated with more primitive areas such as olfactory cortex (JoelWeiner08).

Some workers have distinguished two phenotypes of DA cells organized into a dorsal tier vs. a ventral tier. Roughly, the dorsal tier includes most of the cells of the VTA, but extends laterally into the SNc; the ventral tier includes most of the cells of the SNc, but extends medially to include some (more ventral) cells of the VTA (JoelWeiner00, citing others' work).

More recently, several groups have distinguished as many as four distinct subpopulations of DA cells based on a combination of response patterns to negatively valenced stimuli (i.e., “punishers” and their CSs) and differential projection targets. By far the majority of DA cells seem to still comply with the original “conventional” pattern of response as discovered and promoted by Wolfram Schultz, i.e., that phasic DA responses reflect a consistently valenced reward prediction error (RPE) signal with “bursts” of activity meaning positively valenced “surprise” (occurrence of unexpected positively valenced reinforcement; absence of expected negatively valenced reinforcement) and “dips” meaning negatively valenced surprise (absence of expected positive reinforcement; unexpected negative valence reinforcement). However, it now seems clear that there are one or more much smaller subpopulations that respond to negatively-valenced surprises with bursts. In particular, there seems to be a small ventromedial area of VTA where such cells are located (cite). Different groups have characterized this heterogeneous behavior differently and, currently, it is not clear how these all map to one another. Also, it is not clear how these differing cell populations may map to the dorsal/ventral tier phenotypic distinction mentioned above.

Inputs/Afferents

(Name, and code Strength (L, M, H), Confidence (L, M, H), Transmitter(s))


To a significant degree, the VTA and SNc can be thought of as a single area. There are significant exceptions however. Both VTA and SNc receive afferents from many sources, both subcortical and cortical. Relatively little is known regarding the various contributions of each, e.g., driving, modulatory, inhibitory, etc. Listed here is what appears to the case as of April 2012


Subcortical:

* Lateral Hypothalamic Area (LHA): Glu/excitatory

* Pedunculopontine Tegmental Nucleus (PPTn): Glu/excitory; Ach/both excitatory and inhibitory (cite)

* Central Nucleus of Amygdala (CNA): Glu/excitatory (direct); also projects indirectly via PPTn

* Rostromedial Tegmental area (RMTg): GABAa/inhibitory (cite; confirm)

* Lateral Habenula (LHb): Glu/net inhibitory via VTA GABAa interneurons and/or via RMTg

* Striatum - Patch compartment medium spiny neurons (MSNs): GABAb/shunting inhibitory

* Striatum - Matrix compartment MSNs: GABAa/net excitatory via GABA interneurons

* Globus Pallidus, internal segment (GPi): GABA/inhibitory

* Globus Pallidus, external segment (GPe): GABA/inhibitory

* Substantia Nigra, pars reticulata (SNr): GABA/inhibitory

* Ventral Pallidum (VP): GABA/inhib.

* Dorsal/Ventral Raphe (DR/VR): 5-HT/modulatory?

* Basal Forebrain: Ach/modulatory?

* Locus Coerereus (LC): Norepinephrine/modulatory?


Cortical:

NOTE: All cortical afferents can be assumed to be Glutaminergic/excitatory. However, specific effects might potentially be inhibitory if they were to synapse preferentially onto local GABAergic interneurons.

* Neocortex: all or just part?; especially frontal/PFC/OFC/VMPFC/ACC? (GeislerWise08; details)

* Archicortex: Hippocampus?

* Paleocortex: insula?

Outputs/Efferents

(Name, and code Strength (L, M, H), Confidence (L, M, H), Transmitter(s))

* Ventral Striatum (VS): VTA preferentially projects to VS (Nucleus accumbens (NAc), shell and core; plus ventromedial parts of caudate and putamen)

* Dorsal Striatum (DS): SNc preferentially projects to dorsomedial and dorsolateral striatum, i.e., most of caudate and putamen; also, SNc may have a topological/topographic pattern of connectivity such that parts of SNc may only project to parts of striatum

* Globus Pallidus, internal and external segments; Ventral Pallidum (GPi/GPe/VP): VTA preferentially goes to pallidum

* Substantia Nigra, pars reticulata (SNr): basically same as GPi

* Prefrontal Cortex (PFC): A subset of VTA DA cells project to PFC (“mesocortical” tract)

Functions

Summary list

Function Area 1 [Name]

Effects of stimulation

Effects of lesions/inactivation

Effects of microinjection

Optogenetics

Other

Function Area 2 [Name]

Effects of stimulation

Effects of lesions/inactivation

Effects of microinjection

Optogenetics

Other

Studies activating

Coordinates

Coordinates (x, y, z): [x -y -z]

(???Average of all but Derbyshire, adjusted to midline based on anatomy)

Specific study coordinates (if not too many)

Study Description x y z
NameNameYEAR RVM seed 0 -00 -00
DITTO Placebo > Control late pain 0 -00 -00
DITTO Placebo > Control early pain -00 -00 -00
DITTO Offset analgesia 0 -00 -00

List of Studies

None.

Specific, key studies

Study list: Coordinate based

Neurosynth results for coordinate(s)

None.