NOTICE: Posting schedule is irregular. I hope to get back to a regular schedule as the day-job allows.

Thursday, April 14, 2011

The Gangly Base...

Basal Ganglion

I'm introducing a new term this post - "Ganglion"  - line "nucleus" this denotes a grouping of neurons, in particular, a compact mass of neuron cell bodies. In brain terms, "ganglion" is used interchangeably with "nucleus", although the term "ganglion" has additional meanings in the general body.

The Basal Ganglia (or Basal Nuclei) are structures that are located at the base of the brain, above and to the side of the thalamus.  From this, one might think that the Basal Ganglia develop as part of the diencephalon, like the thalamus and hypothlamaus, but that is not true.  The Basal Ganglia are part of the telencephalon, and developmentally are part of the same formation as the cerebral cortex which forms the "higher" functions of the brain.  So, what are they, and what so they do?

The Basal Ganglia consist of four main structures:  Striatum - so called because of the striped pattern in cross-section due to the projections from thalamus to cortex that pass through the striatum; Globus Pallidus (pallidum) - the "Pale Globe"; Substantia Nigra - named for the darkly-pigmented dopamine-producing neurons; and the Subthalamic Nucleus.  Striatum consists of a dorsal (top) portion termed the Caudate Nucleus, the middle segment is termed Putamen, and the ventral (bottom) portion contains Nucleus Accumbens.  The latter is frequently associated with a Limbic System circuit which includes the Ventral Pallidum and a mesencephalon structure: the Ventral Tegmental Area - this is important, and will be discussed later.

In the brain slice above, the "holes" in the center are the ventricles - they collect and filter thecerebrospinal fluid with cushions the brain and drains waste chemicals from the brain.  The dark masses twoard the center and below the ventricles comprise the basal ganglia.  The white streaks in the Striatum are the axons of the neurons connecting Thalamus (which is behind this slice) and the cortex (dark gray margin lining the surface and folds of the brain).  The gray regions are indeed "Gray Matter" and consist mainly of neuron cell bodies.  The white areas are "White Matter" and consist mostly of axons - they have a waxy coating called "Myelin" which produces the white color.

The major role of  the Basal Ganglia is one of inhibition.  The majority of BG neurons utilize the neurotransmitter GABA (gamma-aminobyutyric acid - blue arrows in diagram at right) which has a suppressive or inhibitory effect at the synapses of targeted neurons.  GABA neurons in Striatum project to GABA neurons in Globus Pallidus (GPe, GPi) and Substantia Nigra (SNr).  GABA neurons in those locations project in turn to thalamus or cortex.  The Pallidal neurons are constantly active, producing a continuous inhibition on their targets.  When the inhibitory Striatum inputs to Pallidum are activated, the inhibition turns *off* the inhibition by Pallidum - a phenomenon called "disinhibition." Since the Thalamus feeds back to the Cortex to regulate muscle movement, the net result is to inhibit the inhibition of Thalamus, and produce hyperactivity of motor movements.  However, there is balance in the circuit (right). The Subthalamic Nucleus (STN) neurons are excitatory (red arrows) and cause a net inhibition of the Thalamus resulting in hypoactivity of motor movements.  This is contradictory, but balanced by dopamine neurons in Substantia Nigra (SNc) which modulate the Striatum, balancing the inhibitory and excitatory effects of motor neurons.

...and this can lead to problems.  Parkinson's Disease results in loss of the Dopamine neurons in Substantia Nigra, causing the Basal Ganglia to "stick" in one state or the other, leading to tremors (hyperactivity) or extreme rigidity and difficulty initiating movements (hypoactivity).  There are numerous movement-related disorders associated with damage to or misfunction of the Basal Ganglia (Cerebral Palsy, Huntington's Disease, Parkinson's, Chorea, twitches, tics, etc.).  Other diseases, syndromes and disorders include Attention Deficit/Hyperactivity Disorder, Tourette's Syndrome, and Obsessive Compulsive Disorder.

This leads to the second major role of BG - motivation.  Parkinson's patients have difficulty *motivating* their bodies to move, but there are other aspects of motivation as well. The Limbic Basal Ganglia - Nucleus Accumbens (NA), Ventral Pallidum (VP) and Ventral Tegmental Area (VTA) are involved in emotional and risk-reward associated motivation as well.  NA and VP act similar to Striatum and GP with inhibitory projections in this role, with VTA acting in the Substantia Nigra role to provide Dopamine producing neurons.
This latter circuit is particularly important in behavior and memory research, because it has been shown to be involved in individual judgment of reward, resulting in the willingness of a subject to perform behavioral tasks and receive a reward or reinforcement for that behavior.

In Science Fiction, this circuit has been immortalized as the "Brain Reward Circuit."  Author Larry Niven wrote of patients with electrodes in their brain that would choose electrically-generated pleasure over any other type of reward.  Likewise Spider Robinson included a similar "addiction" in some of his stories.  In current neuropsychological research,  the limbic Basal Ganglia are associated with drug abuse due to the fact that Dopamine levels are easily altered by cocaine, amphetamine, methamphetamine and other drugs.

However, in the interest of time and space, these matters will be discussed in a later blog as we cover various brain diseases and disorders.  Next up we will close the section on parts of the brain with a discussion of the one part that is not considered physically part of the brain:  the spinal cord.

Until next time, take care of your brain...

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