Medium spiny neuron

The medium spiny neurons are a special type of inhibitory cells representing approximately 75% 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.

Appearance and Location
The medium spiny neurons are medium sized neurons with large and extensive dendritic trees. Each branch of the 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 ncl. accumbens - is the main input station of the basal ganglia. Medium spiny neurons in this structures 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. But there seem to be functional differences as well in that those neurons receive different cortical input. In histological examination one can identify small clusters of medium spiny neurons of one type (called "patches" or "striosomes") embedded in a surrounding "matrix" containing medium spiny cells of the other type.

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 axons forms contacts with many spiny neurons and each spiny neurons receives a vast amount of inputs from different incoming axons. Since these inputs are Glutamatergic they exhibit an excitatory influence on the inhibitory medium spiny neurons.

There is also a big amount of interneurons originating in different areas which regulate the excitability of the medium spiny neurons. The synaptical connections between the spiny neurons and the interneurons are typically close to spiny neurons' cell soma. Recall that excitatory postsynaptic potantials caused by Glutamatergic inputs at the dendrites of the spiny neurons only cause an action potential when strong enough on entering the cell soma. Since the 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. As a result, the excitatory input coming from cortical etc. neurons has to be very strong respectively caused by many simulaneously arriving excitations.

In consequence the medium spiny neurons are usually quiet and do not exhibit any spontaneous activity unless sufficiently activated.

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 send axons to the subst. 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 gloubus pallidus are also inhibitory, thus inhibting the excitatry 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 absence of cortical stimulation, SNpr and VTh neurons are tonically inhibited thus preventing involuntary sponanteous 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 which is net excitement causing them to activate upper motor neurons commanding a movement. Cortical activition of the basal ganglia thus eventually results in excitement (disinhibition) of motor neurons causing movement to take place.

Indirect pathway
In the indirect pathway, excitatory 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 segmemt 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.