How many levels is neural function integrated on?
What are these levels?
Spinal, Supraspinal and Cortical
What is the highest level of neural integration?
The cerebral cortex exerting control over our all our sensory and motor systems
What are the four main neurotransmitters that the distinct systems of the brain are centred on?
What is the centre of our emotional expression and is also important for coding memories?
The limbic system
How is the brain physically protected?
The skull, CSF
The Blood Brain Barrier
What are the three levels of integration (lowest to highest) and what do they govern?
- Homeostasis and REFLEX actions
Simplest level of neural activity: basic locomotory circuits, postural control, stereotypical behaviour
- Primitive actions: feeding, drinking, sexual and instinctual activities
Medial and Ventral SC Paths (+ medial cerebellum), Proximal Limbs, Proximal Limbs. PHYLOGENETICALLY OLD
- Science, Philosophy, Art
Lateral SC pathways (+ lateral cerebellum), distal limbs, PHYLOGENETICALLY NEW
intellect, personality, cognition
What can norephinephrine/noradrenaline be classed as?
Where can norephinephrine be found elsewhere in the body?
In the autonomic nervous system as the neurotransmitter found postsynaptically in the sympathetic nervous system, and also secreted as a hormone by the adrenal medulla
In the CNS, where are the cell bodies of the noradrenergic neurons located?
In the Locus Ceruleus of the medulla.
Where do the axons travel to once they have left the locus coeruleus?
What do they activate?
What do they function in?
axons descend down the spinal cord, enter the cerebellum and innervate the entire neocortex.
α receptors (noradrenaline has more affinity
β receptors (adrenaline has more affinity)
Stress, general arousal and alertness, mood
(elevated levels increase mood)
What is serotonin also known as?
What are the serotonin receptor types?
Where are the Serotonin containing neurons found originating from?
Where do the projections travel to?
The Raphe Complex in the brainstem
the hypothalamus, the limbic system, the cerebellum and the spinal cord
Where do antidepressant drugs act upon?
5HT6 receptor family types
Where do many non-liscensed drugs act upon? (ecstacy and LSDs - hallucinogens)
These exert their affects by acting on seratonergic neurons
What can dopamine be classed as?
What are the two systems associated with Dopamine?
nigrostriatal system involved in motor control (basal ganglia)
mesocortical system, projecting to the limbic cortex, associated with reward behaviour and addiction.
the neurons of which are located in several brain regions making up the nigrostriatal system involved in motor control (basal ganglia) and the mesocortical system, projecting to the limbic cortex, associated with reward behaviour and addiction.
What are dopaminergic neurons implicated in the pathophysiology of?
Parkinsonism (dopaminergic neuron degeneration)
Schizophrenia (overstimulation of dopaminergic receptors)
- They have also been associated with Tourettes syndrome (Mozart being hypothesized as a sufferer).
Where is Acetylcholine found? (outside brain)
- neurotransmitter at neuromuscular junctions (NITOTINIC cholinergic receptors)
- autonomic ganglia (both symp and parasymp),
- the majority of parasympathetic postganglionic nerve terminals (MUSCARINIC cholinergic receptors).
Where are the neurons of acetylcholine found in the brain?
- basal forebrain complex
- the pontomesencaphalic cholinergic complex (muscarinic AND nicotinic cholinergic receptors).
What are Ach Fibres known to be involved in the regulation of?
Ach fibres are known to be involved in regulation of sleep-wake cycles, learning and memory.
Where do the fibres from the NUCLEUS BASALIS of MEYNERT project to?
What are these involved in?
The amygdala and the entire neocortex
Perception, memory, motivation and cognition.
What is the pathophysiology of Alzheimers?
There is extensive loss of the Ach fibres (from Nucleus Basalis of Meynert) giving rise to the memory loss seen with this and the other characteristic symptoms of the condition
Discuss the brain hierarchy
Spinal cord and medulla are the phylogenetically oldest
•Reflexes, Vegetative fxn
•Emotions, Allocortex and juxtallocortex
Cerebrum - phylogenetically newest
What is the limbic system composed of?
rings of tissue lining the inside of the neocortex
What does 'limbic' mean?
Who first described it?
What two systems can it be divided into?
(loose anatomical and functional classification)
Limbic = “ring”
Broca 1878, Papez, 1937
Hippocampal and Amygdaloid
What is the hippocampal system composed of?
of the limbic cortex in the cingulate gyrus, the hippocampus, fornix, mammilary body and anterior thalamus.
Where did the knowledge about the hippocampal system arise from?
How is this condition characterised?
What is it caused by?
Korsakoffs syndrome (Papez, 1937)
Retrograde (memory loss) and anterograde amnesia (inability to form new memories) and confabulation
Caused by alcoholic destruction of the mamillary bodies and anterior thalamic structures.
What are the functions of the hippocampal system?
Interface of intellect and emotion
Formation of new memories
In animals, what does damage to the hypothalamic nuclei result in?
What does damage to the amygdala in experimental animals cause?
Huge difficulties in emotional expression such as hypersexuality and hypoemotionality.
What is the amygdaloid and olfactory region of the limbic system composed of?
What are they concerned with?
the amygdala, the olfactory bulbs, medial forebrain bundle
Emotional expression ( fear, anxiety, placidity, sexual drives). Add an emotional component to memories (classical and operant conditioning), and neurons in this area are thought to strengthen the engram (memory consolidation). (This is why smells often stimulate nostalgia, with the olfactory bulbs an integral part of this pathway).
In humans, disruption to the amygdala is implicated in what conditions?
What other things can we consider?
Borderline Personality Disorder, Bipolar disorder and social phobias.
Motivation and reward
•Bar pressing expts - electrodes and tension relief
What are the layers protecting the brain?
•Skull, dura and arachnoid
•Cerebro spinal fluid (cushioning)
How much does the brain weigh with and without the aid of CSF?
This allows the relatively flimsy attachments between the brain and the skull to attach it very effectively.
Where is CSF produced?
Where does it travel to and end up?
Choroid Plexus of the cerebral ventricles
travels through the ventricles, down the spinal cord. It drains back to the blood via arachnoid granulation to superior sagittal sinus, or via spinal nerve roots, or via olfactory tracts.
Where is CSF retrieved?
Retrieved at nerve roots, olfactory tracts superior saggital sinus
What is the complete volume of CSF?
How much is produced per day?
500ml per day
(turned over 3.7 times per day)
What is the function of CSF?
What can result when too much is produced?
- provide mechanical support and protection for the brain (cushioning)
- helps maintain a constant external environment and to serve as a cerebral lymphatic system.
What is the Blood Brain Barrier?
- No fenestrations in capillaries
- Tight basement membrane
- Tight junctions between ednothelial cells of cerebral caps and epithelial cells of the brain and choroid plexus
What is the function of the blood brain barrier?
What are the practical consequences of this?
- an extra line of defence, preventing even minor changes in ion concentration upsetting the excitability of neurons.
- prevents overstimulation of the brain by blood borne toxins that are readily digestable.
For drug therapy we need to use drugs that are fat soluble, or have specific carriers.
What substances can cross the BBB?
Bacteria (but spirochetes)
Immune cells (with inflammation)
Small, fat soluble molecules
Essential nutrients use membrane transporter protein
Larger drugs may penetrate BBB if they can use a carrier
Give examples of substances that CANNOT cross the BBB?
Large molecules do not pass through the BBB easily.
Low lipid (fat) soluble molecules do not penetrate into the brain. However, lipid soluble molecules, such as barbituate drugs, rapidly cross through into the brain.
Molecules that have a high electrical charge are slowed.
Where is there no BBB?
•Vomiting centre (area postrema)
(Classified as Circumventricular organs)
Vomiting Centre = because it senses toxins in the blood that the other parts of the brain are protected from. The area postrema triggers nausea and vomiting to prevent further ingestion of toxins.
Hypothalamus = The median eminence of the hypothalamus connects the hypothalamus to the pituitary gland. The median eminence is not covered by the blood brain-barrier because hormones secreted by the pituitary gland collect in this region before being secreted into the bloodstream.