Medium spiny neuron

Medium spiny neuron
Details
Location Basal Ganglia
Morphology Spiny neuron
Function inhibitory projection neuron
Neurotransmitter GABA
Presynaptic connections Cortex, thalamus, & brain stem
Postsynaptic connections Other basal ganglia
Identifiers
NeuroLex ID Medium Spiny Neuron
Anatomical terminology

Medium spiny neurons (MSN), also known as spiny projection neurons, are a special type of GABA-ergic inhibitory cell representing 90-95% (depending upon species) of the neurons within the corpus striatum of the basal ganglia. They play a key role in initiating and controlling movements of the body, limbs, and eyes.

Medium spiny neurons have dopamine receptors. Dopamine has a dual action on MSNs. It inhibits the (D2-type) MSNs in the indirect pathway and excites (D1-type) MSNs in the direct pathway. Consequently, when dopamine is lost from the striatum, the indirect pathway becomes overactive and the direct pathway becomes underactive.

Appearance and location

The medium spiny neurons are medium sized neurons (~15 microns in diameter) with large and extensive dendritic trees (~500 microns in diameter).[1] Each branch of these dendritic trees is packed with numerous small spines which receive synaptic inputs from neurons outside the striatum. The corpus striatum - consisting of nucleus caudatus, putamen, and nucleus accumbens - is the main input station of the basal ganglia. Medium spiny neurons in this structure receive cortical, thalamic and brain-stem inputs. In fact, the whole human neocortex except the primary visual and primary auditory cortex project to the striatum.

Within the striatum, there are at least two different types of medium spiny neurons. These types were first distinguished because of the different neuropeptides they contain. About half the spiny cells express substance P, dynorphin and dopamine D1 receptors and project to the internal globus pallidus and pars reticulata (the direct pathways) whereas the other half express enkephalin and the dopamine D2 receptor and project to the external globus pallidus (the "indirect pathway").[2] With different types of immunocytochemical or histochemical staining one can identify small clusters (150-300 µm in diameter) of medium spiny neurons (called "patches" or "striosomes" - making up about 15% of the volume of the neostriatum) embedded in a surrounding "matrix" (making up about 85% of the volume of the striatum).[3]

Function

The medium spiny neurons are GABAergic neurons and hence have an inhibitory influence on the neurons they project to. Within the basal ganglia, there are several complex circuits of neuronal loops all of which include the medium spiny neurons (for further information see basal ganglia). They send axons to the internal and external segment of the globus pallidus as well as the substantia nigra pars reticulata.

The cortical, thalamic, and brain-stem inputs that arrive at the medium spiny neurons show a vast divergence in that each incoming axon forms contacts with many spiny neurons and each spiny neuron receives a vast amount of input from different incoming axons. Since these inputs are glutamatergic they exhibit an excitatory influence on the inhibitory medium spiny neurons.

There are also a large number of interneurons in the striatum which regulate the excitability of the medium spiny neurons. The synaptic connections between a particular GABAergic interneuron, the parvalbumin expressing fast-spiking interneuron, and spiny neurons are close to the spiny neurons' soma, or cell body.[4] Recall that excitatory postsynaptic potentials caused by glutamatergic inputs at the dendrites of the spiny neurons only cause an action potential when the depolarization wave is strong enough upon entering the cell soma. Since the fast-spiking interneurons influence is located so closely to this critical gate between the dendrites and the soma, they can readily regulate the generation of an action potential. Additionally, other types of GABAergic interneurons make connections with the spiny neurons. These include tyrosine hydroxylase[5][6] and neuropeptide-Y expressing interneurons.[7][8]

Direct pathway within the basal ganglia

The direct pathway within the basal ganglia makes excitatory inputs coming from e.g. the cortex cause a net excitation of upper motor neurons in the motor areas of the cortex. In the direct pathway, the medium spiny neurons project to the internal division of the globus pallidus which in turn sends axons to the substantia nigra pars reticulata (SNpr) and the ventroanterior and ventrolateral thalamus (VTh). The SNpr projects to the deep layer of the superior colliculus thus controlling fast eye movements (saccades). The VTh projects to upper motor neurons in the primary motor cortex (precentral gyrus).

Neurons in the globus pallidus are also inhibitory, thus inhibiting the excitatory neurons in the SNpr and VTh. But in contrast to the medium spiny neurons, globus pallidus neurons are tonically active when not activated. Thus in the absence of cortical stimulation, SNpr and VTh neurons are tonically inhibited thus preventing involuntary spontaneous movements.

Once the medium spiny neurons receive sufficient excitatory cortical input, they are excited and fire a burst of inhibitory action potentials to globus pallidus neurons. These tonically active neurons are then inhibited, causing their inhibitory influence on SNpr and VTh to decline. Thus SNpr and VTh neurons are disinhibited resulting in net excitement causing them to activate upper motor neurons commanding a movement. Cortical activation of the basal ganglia thus eventually results in excitement (disinhibition) of motor neurons causing movement to take place.

Indirect pathway

In the indirect pathway, excitation (e.g. cortical input to the basal ganglia) results in net inhibition of upper motor neurons. In this pathway the medium spiny neurons in the striatum project to the external segment of the globus pallidus. These neurons in turn project to the internal segment of the globus pallidus and to the subthalamic nuclei which form a closed loop by projecting back to the internal globus pallidus.

Cortical excitement of medium spiny neurons causes them to inhibit external globus pallidus neurons. These tonically inhibiting neurons thus decrease their inhibitory influence on the internal globus pallidus and the subthalamic nuclei.

Let's first look at the internal globus pallidus neurons which are also tonically inhibiting VTh and SNpr neurons. Since the inhibitory influence from the external globus pallidus is now reduced, these neurons show stronger activity thus increasing their inhibition of SNpr and VTh neurons.

The projections of the external globus pallidus to the subthalamic nuclei causes these neurons to increase their firing rate, since the globus pallidus neurons are inhibited by medium spiny neurons. The subthalamic nuclei have excitatory projections to the internal globus pallidus thus causing the internal globus pallidus neurons to increase their inhibititory influence on SNpr and VTh.

Eventually excitatory inputs from the cortex results in net inhibition of upper motor neurons thus preventing them from initiating a movement.

Notes

  1. ↑ Kawaguchi Y1, Wilson CJ, Emson PC. Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. J Neurosci. 1990 Oct;10(10):3421-38. PMID 1698947
  2. ↑ Wilson, C.J. (2004) Basal Ganglia In: G. M. Shepherd (ed.) The Synaptic Organization of the Brain, 5th Edition. Oxford University Press, Oxford, pp. 361-414.
  3. ↑ Gerfen, CR, Wilson, CJ (1996) The basal ganglia. In: Handbook of Chemical Neuroanatomy, Vol. 12: Integrated Systems of the CNS, Part III (L.W. Swanson, A. Bjorklund, T Hökfelt, Science BV, Amsterdam, pp 371-468.
  4. ↑ Tepper JM, Wilson CJ, Koós T. Brain Res Rev. 2008 Aug;58(2):272-81. Epub 2007 Nov 1. PMID 18054796
  5. ↑ Ibáñez-Sandoval O, Tecuapetla F, Unal B, Shah F, Koós T, Tepper JM. J Neurosci. 2010 May 19;30(20):6999-7016. doi: 10.1523/JNEUROSCI.5996-09.2010. PMID 20484642
  6. ↑ Tepper JM, Tecuapetla F, Koós T, Ibáñez-Sandoval O. Front Neuroanat. 2010 Dec 29;4:150. doi: 10.3389/fnana.2010.00150. PMID 21228905 [PubMed]
  7. ↑ English DF, Ibanez-Sandoval O, Stark E, Tecuapetla F, Buzsáki G, Deisseroth K, Tepper JM, Koos T. Nat Neurosci. 2011 Dec 11;15(1):123-30. doi: 10.1038/nn.2984. PMID 22158514
  8. ↑ Ibáñez-Sandoval O, Tecuapetla F, Unal B, Shah F, Koós T, Tepper JM. J Neurosci. 2011 Nov 16;31(46):16757-69. doi: 10.1523/JNEUROSCI.2628-11.2011. PMID 22090502

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