LOCALIZATION OF NEUROTRANSMITTER SYSTEMS

       ALL NEUROTRANSMITTER SYSTEMS ARE
          LOCALIZED TO VARYING DEGREES

            For example, neurons which release a specific
               neurotransmitter such as dopamine are often:

                 restricted by ORIGIN to one or a few cell
                    clusters or NUCLEI in the brain

                 Restricted by projection or target to certain
                    brain regions or cell types

                 And in turn are PROJECTED UPON by
                    restricted non-dopaminergic brain regions

            Receptor sub-types are also LOCALIZED

       FUNCTION IS ALSO SPECIFIC TO LOCAL REGIONS
          OR SYSTEMS

            WARNING: the function which is localized is neural
               function NOT BEHAVIOR.... 

          EXAMPLE: understanding computer hardware helps very little in 
trouble-shooting most software problems Sometimes the function is linked 
through a family of behaviors!

       MULTIPLICITY OF SYSTEMS

            Sometimes a single neurotransmitters is used in a
               number of functionally distinct systems

            And a single system typically incorporates a
               number of different neurotransmitters

                 Indeed, even a single neuron releases
                    SEVERAL neurotransmitters, and targets a
                    wide range of receptor types

  THE DOPAMINE SYSTEMS

       THERE ARE 4 SYSTEMS OF PHARMACOLOGICAL
          INTEREST:

            The most important is the forebrain dopamine
               system, which has two subdivisions:

               1. The nigrostriatal system

               2. The mesolimbic system

            Two much more limited systems are:              
               3. The tuberoinfundibular system

               4. The medullary vomiting system

       THE NIGROSTRIATAL DOPAMINE SYSTEM

            Cells of origin: located in the ventral mesencephalon
               in a half-moon shaped nucleus called the SUBSTANTIA NIGRA

                 NIGRA (black) because over time there is
                    accumulation of a blackish metabolic by- product in the 
                    neurons

            Project to: the striatum, that is the caudate nucleus
               and related parts of the basal ganglia

            Function: poorly understood

                 called the EXTRAPYRAMIDAL MOTOR
                    SYSTEM because damage here caused odd movement disorders, 
                    including Parkinson's

                 Not about movement so much as
                    MOTIVATION, choosing among and between various motor 
                    programs over-stimulation causes STEREOTYPY,
                    becoming locked into repetitive motor routines

                 AND is a part of the larger reward system of the
                    brain, in that motivation and reward are certainly linked

       THE MESOLIMBIC DOPAMINE SYSTEM

            Cells of origin: a more diffuse collection of dopamine
               neurons in the ventral mesencephalon, medial to
               the substantia nigra

                 Called the VENTRAL TEGMENTAL AREA,
                    usually abbreviated VTA

            Projects to the Nucleus Accumbens, a ventral region
               of the basal ganglia

                 AND to other, larger forebrain regions, including

                    + the hippocampal system

                    + the amygdala

                    + prefrontal cortex

            Function: mediates the emotional side of motivation,
               things like euphoria


       THE TUBEROINFUNDIBULAR DOPAMINE SYSTEM
          
            Big name, small system, in the "neck" of tissue
               connecting the hypothalamus and pituitary

            Inhibits release of prolactin

       THE MEDULLARY VOMITING CENTER

            dopamine plays a secondary role in stimulating
               vomiting

  THE SEROTONIN SYSTEM(S) OF THE BRAIN

  ORIGIN: a relatively small number of neurons in the pons

            The raph‚ nuclei: a vertical BAND of serotonergic
               cell bodies just on the midline in the pons

       PROJECTS TO: virtually all parts of the brain

       FUNCTION: A mystery, but evidently rather calming or
          inhibitory, including:

            Helps induce sleep

            Seems to inhibit appetite

            Including sexual appetite/libido

            also inhibits aggression

            and body temperature

  THE NOREPINEPHRINE SYSTEM

       ORIGIN: A small, densely packed paired nucleus on the
          dorsal bank of the pons called the LOCUS COERULEUS

            Literally the blue spot - blue for the same reason the
               Substantia Nigra is nigra

       PROJECTS TO: Like the raph‚, just about everywhere

            and in many regions receiving BOTH serotonergic
               and noradrenergic projections, they seem to have opposite 
               effects

       FUNCTION: Again poorly understood, but seems to
          involve:

            Excitation

            Inhibition of sleep

            Enhanced arousal and awareness

            and perhaps fear

  THE ACETYLCHOLINE SYSTEMS:

       There are a number, we will consider three:

       THE BASAL FOREBRAIN SYSTEM: 

            A thin layer of acetylcholine neurons at the base of
               the brain, anterior to the hypothalamus

            Important for arousal and memory

            destroyed in Alzheimer's disease

       THE PONTINE AROUSAL/REM SYSTEM

            Part of the REM sleep system

            Seems responsible for heightened activity in the 
               visual systems of the brain during dreaming

       INTERNEURONS IN THE BASAL GANGLIA

            Dopaminergic neurons from the substantia nigra
               synapse on acetylcholine interneurons in the striatum

  THE GABA SYSTEMS:

       VERY WIDESPREAD

            Inhibitory interneurons everywhere

            Will consider a few of the more important systems:

       GABA IN THE CEREBELLUM

            Helps explain loss of coordination caused by alcohol

       GABA IN THE BASAL GANGLIA

            Unlike most places in the brain, feedback projections
               from the basal ganglia to the substantia nigra use GABA

       GABA AND SEIZURES

  SYSTEMS SUPPORTING EMOTION:

       FEAR AND ANXIETY

            Prefrontal Cortex

            The Amygdala

            Locus Coeruleus

            The GABA system 

       REWARD AND EUPHORIA

            The Dopamine System

            Prefrontal cortical control of the dopamine system