Neurotransmitters

Cholinergic System:

• Cholinergic synapses utilize acetylcholine (ACh) as neurotransmitter

• can be excitatory OR inhibitory (not both)

• found throughout CNS and PNS

• has two categories:

  • Nicotinic ACh Receptors: Always excitatory

    • use ligand-gated channels

    • acetylcholine (neurotransmitter) acts as ligand that binds to ligand gated channels

      • causing Na+ to rush into cell body, moving down concentration gradient

        • causes depolarization

          • leading to EPSP

            

  • Muscarinic ACh Receptors: can be excitatory or inhibitory

  • use secondary messenger systems called G-Protein

  • acetylcholine binds to receptor

    • causes G-Protein to disassociate and bind to K+ channels, causing it to open

      • K+ exits the cell, moving down concentration gradient

        • causes cell body to become more negative, leading to hyper-polarization

          • leading to IPSP

  • depending on what type of neurotransmitter binds, this will determine whether the neuron becomes more excitatory (EPSP) or inhibitory (IPSP)

• Synaptic Clearing of Acetylcholine (ACh)

  • if release neurotransmitter into synapse and leave it there, it will continuously stimulate

  • must be cleared

    • two ways neurotransmitters are cleared from synaptic membrane:

      • Acetylcholinesterane (AChE): enzyme used in post synaptic membrane that breaks down Acetylcholine to make it chemically inactive

        

    • Reuptake: the process by which neurotransmitters are absorbed back into the presynaptic neuron after their release, via endocytosis

      • there are medications (anti-depressants) that affect reuptake

        • prevent neurotransmitters from being reabsorbed by the presynaptic neuron

          

• Cholinergic synapses also utilize Monoamines

  • Monoamines: regulatory molecule derived from amino acids

    • 4 types of Monoamines:

      • dopamine

      • epinephrine

      • serotonin

      • norepinephrine

        • uses secondary messenger called G-Proteins

        • also a hormone when released in blood, but when released in synapse, it is a neurotransmitter

        • cleared from the synaptic cleft by reuptake

Other Neurotransmitters

• Glutamate: excitatory neurotransmitter

  • an amino acid used as the major neurotransmitter in the brain (CNS)

  • produces EPSPs in 80% of synapses in cerebral cortex

• GABA: inhibitory neurotransmitter

  • most common neurotransmitter in brain

  • produces IPSPs by binding open Cl- channels, causing influx of Cl-

    • leads to hyper-polarization

      

• Glycine: inhibitory neurotransmitter

  • produces IPSPs by binding open Cl- channels, causing influx of Cl-

    • leads to hyper-polarization

Neurotransmitters responsible for subconscious control of skeletal muscle:

• excitatory neurotransmitters responsible for subconscious control of skeletal muscle:

  • Glutamate neurotransmitters

  • Dopamine neurotransmitters

• inhibitory neurotransmitter responsible for subconscious control of skeletal muscle:

  • GABA neurotransmitters

Relationship of Motor Circuit to Parkinson’s disease

• Nigrostriatal System includes the Dopaminergic pathway

• Dopaminergic pathway: neurons in circuit releases dopamine into synapses

  • Parkinson's disease: death of neurons that release dopamine in Substantia Nigra

    • symptoms include loss of control of skeletal muscle

      • dopamine is still sent to Substantia Nigra but neurons are dead so neuron does not get command, and communication is not in tact with skeletal muscle

Relationship of Motor Circuit to Huntington’s disease

• Huntington's Disease: death of neurons releasing GABA in the Caudate Nucleus due to genetic defect

  • effects inhibitory pathways

    • when GABA is released into synapse, caudate nucleus’ neurons are dead and cannot react to it to prevent inhibitory mechanism, so antagonist muscle still contracts when should be inhibited to allow agonist muscle to contract

      • symptoms include spastic motion of limbs and facial muscles, abnormal muscle contractions

Mesolimbic pathway in Limbic System:

• Mesolimbic system includes a dopaminergic pathway

  • reward pathway, actions cause someone to feel good

    • related to drug use making one feel good

      • plays a crucial role in the reinforcement of behaviors that are perceived as pleasurable, which can lead to patterns of addiction when drugs artificially stimulate these reward pathways.

Neurotransmitters in Autonomic Nervous System

Cholinergic Responses

Cholinergic Responses always release ACh

• use Acetylcholine (ACh) Nicotinic Receptors

  • ACh binds to Nicotinic Receptors, using ligand-gated channels

  • always excitatory

  • Excitatory Response to Acetylcholine (ACh) Nicotinic Receptors:

    • causes depolarization in:

      • Skeletal muscle

        • producing action potentials and muscle contraction

      • autonomic ganglia

        • all autonomic ganglia have ACh nicotinic receptors (both sympathetic and non-sympathetic nervous system)

          • causes activation of post ganglionic neurons

• use Acetylcholine (ACh) Muscarinic Receptors

  • ACh binds to Muscarinic Receptors, using G-proteins

  • ALL parasympathetic and few sympathetic effector synapses in autonomic nervous system

  • either excitatory or inhibitory

    • Excitatory Acetylcholine (ACh) Muscarinic Receptors (M3 or M5):

      • causes depolarization in smooth muscle and glands:

        • contracting of smooth muscle

        • stimulating secretion of glands

    • Inhibitory Acetylcholine (ACh) Muscarinic Receptors:

      • causes hyperpolarization in heart

        • slowing of heart rate

          

Adrenergic Responses

Adrenergic Responses release Norepinephrine

• almost all sympathetic effector synapses are Adrenergic (bind norepinephrine)

  • adrenergic responses cause epinephrine to be released into the blood from adrenal glands and norepinephrine to be released from sympathetic nerve endings

• Norepinephrine binds to 3 major categories of adrenergic pathways:

  • Adrenergic Alpha Receptors

    • Adrenergic Alpha-1 Receptors: cause vasoconstriction in viscera and skin

      • vasoconstrictor effect of the sympathetic nerves always result from activation of alpha-adrenergic receptors

  • Adrenergic Beta Receptors:

    • Adrenergic Beta-1 Receptors: cause increased heart rate and contractility (how hard contraction is)

      • example: beta blockers bind to beta-1 receptors to keep heart rate low

    • Adrenergic Beta-2 Receptors: cause dilation of bronchioles and blood vessels

  • all Adrenergic receptors bind via G-proteins