Download Neuroscience 14c – The Limbic System and Drugs of Abuse

Neuroscience 14c - The Limbic System and Drugs of Abuse
Anil Chopra
1. Olfactory system
2. Review of limbic structures
3. Anatomical basis of emotion
a. Memory and learning
b. Fear and anxiety
c. Anger and aggression
d. Reinforcement and reward
4. Drug dependence pathway
Olfactory System
- “Smell”
- can detect 2000-4000 different odours.
- There are 3 main types of cell in the olfactory
system which we progressively lose with age:
o bipolar olfactory neurons
o sustentacular cells
o basal cells
- There are over 1000 different sub-types of receptor cell in the nasal passage, each
is able to detect a different chemical.
- The “smell” that we perceive comes from the combination of the different
chemical in the substance.
The olfactory pathways consist of:
 Olfactory receptor cells which pass through the roof of the nose through a
perforated bone called the cribriform plate into the olfactory bulb.
 The olfactory bulb is in the oribito-frontal cortex and it contain contains
o Olfactory neurons – synapse in the…
o Glomeruli – which have neurones forming the…
o Olfactory tract
 The neurons from the olfactory tract can synapse in a number of places
o Olfactory tubercule  thalamus
o Pyriform cortex
o Amygdala
o Entorhinal cortex  hippocampus.
o Anterior olfactory nucleus  Contralateral Pyriform cortex and olfactory
tubercule
Defects in olfaction or olfactory pathways can result in anosmia – the inability to
smell.
Limbic System
The limbic system contains many parts all of which are interrelated. The system
responsible for this processes aimed at survival:
o maintenance of homeostasis via activation of visceral effector
mechanisms, modulation of pituitary hormone release and initiation of
feeding and drinking
o agonistic (defence & attack) behaviour
o sexual & reproductive behaviour
o memory
 The pre-dominant outflow of the limbic system is to the pre-frontal cortex and
hypothalamus as well as to the cortical areas involved in planning of behaviour
and motor responses
 Thus the limbic system has a role in attaching a behavioural significance and
response to a stimulus – especially in respect to emotional content
Put simply:
hypothalamic mammillary bodies → anterior nucleus of the thalamus → cingulate
gyrus → parahippocampal gyrus → entorhinal cortex → hippocampus → fornix →
hypothalamus
Cingulate Gyrus: receives input from the anterior nucleus of the thalamus and the
neocortex and projects onto the parahippocampal gyrus via the cingulum.
Parahippocampal Gyrus: part of the brain that contains entorhinal and perihinal
cortices.
Entorhinal Cortex: an important memory and learning centre in the brain especially
for classical conditioning. It receives inputs from a number of different senses and
projects onto the hippocampus.
Hippocampus: a part of the forebrain, located in the medial temporal lobe. There is
one on each side of the brain projecting onto the fornix/fimbria. It receives input from
the perforant pathways.
Fornix: the fornix is a C-shaped bundle of fibres that project from hippocampus to the
mammilary bodies. It splits and forms, on either side of the brain, the 2 crus of the
fornix. These then join together in the midline of the brain to form the body of the
fornix which then splits again into the 2 columns of the fornix to project onto the
mammillary bodies.
Mammillary Bodies: two round bodies on the anterior of the fornix which form part
of the limbic system. They contain two sets of nuclei, the lateral mammillary nuclei
and the medial mammillary nuclei. They receive input from the hippocampus and the
amygdala and project onto the thalamus via the mamillo-thalamic tract.
Amygdala: groups of neurones in the medial temporal lobes. These are subdivded:
 Basolateral complex – receive impulses from a number of sensory systems it is
split into
 Later
 Basal
 Accessory
 Centromedial nuclei - receive impulses from a number of sensory systems.
 Cortical nucleus – receives information from olfactory bulb and olfactory nuclei.
These project into the hypothalamus via the stria terminalis and the ventral
amygdalofugal pathway. It also projects onto the reticular nucleus for increased
reflexes, to the nuclei of the trigeminal nerve and facial nerve for facial expressions of
fear, and to the ventral tegmental area, locus coeruleus, and laterodorsal tegmental
nucleus for activation of dopamine, noradrenaline and adrenaline.
Septum: lies beneath the rostral corpus callosum. Receives input from the amygdala,
olfactory tract, hippocampus and brainstem. It projects onto the stria medularis
thalami, hippocampus and hypothalamus. It is involved with reward and
reinforcement of behaviours.
The Papez circuit is a
pathway of the limbic
system that is used to
explain emotional
behaviour.
brain systems involved
in fear & anxiety, anger
& aggression and
reinforcement & reward
Emotional colouring
Neocortex
Emotional experience
Cingulate
cortex
Anterior Nucleus
of Thalamus
Cingulum bundle
Hippocampus
Fornix
MTT
Hypothalamus
Emotional expression
Fear and Anxiety:
 Principally due to the Amygdala
 A small almond shaped structure in the medial aspect of the temporal lobe
 Involved in the learning and storage of the emotional aspects of expierence
 Afferent connections – olfactory cortex, septum, temporal neocortex,
hippocampus, brainstem
 Efferent connections – stria terminalis
 Clinical – Kluver-Bucy Syndrome
Aggression:
 “Sham Rage”
 Structures shown to be associated with aggression:
 Hypothalamus
 Brainstem – periqueductal grey matter
 Amygdala
Reinforcement and Reward:
 Principally due to the Septum
 Afferent connections – amygdale, olfactory tract, hippocampus, brainstem
 Efferent connections – stria medularis thalami, hippocampus, hypothalamus
Memory and Learning:
 Principally due to the hippocampus:
 Afferent connections – perforant pathway
 Efferent pathways – Fimbrial/fornix
Clinical – Alzheimar’s disease, Parkinson’s
Clinical Conditions
Alzheimer’s Disease
Can manifest itself in the hippocampus. It is caused by plaques in the region and can
spread making it a degenerative disease. It normally starts in the hippocampus and
entorhinal cortex and spread to the parietal lobe and the frontal lobe:
 Early
– Hippocampus and entorhinal cortex
– Short-term memory problems
 Moderate
– Parietal lobe
– Dressing apraxia
 Late
– Frontal lobe
– Loss of executive skills
Kluver-Bucy Syndrome
Caused by defects in the amygdala. It can cause:
– Loss of fear
– Visual agnosia – inability to recognise objects
– Hyperorality – inappropriate exploratory behaviour
– Hypersexuality – inappropriate sexual behaviour
Anger and Aggression
The hypothalamus, brainstem and amygdala are all shown to associate with feelings
of anger and aggression. Defects can result in “sham rage” – easy aggregation by
provocation. 5-HT (serotonin) in raphe nuclei are also associated with anger.
Drug Dependence
Dependence on drugs is associated with the Mesolimbic
dopaminergic pathway. The dompaminergic cells cause the
release of dopamine which travels along the median forebrain
bundle to 3 main structures: the cortex, nucleus accumbens and
the amygdala. The dopamine may have several effects including
euphoria. Repeated exposure can lead to dependence due to a
lessened effect of dopamine (caused by down-regulation of
dopamine receptors). Opiates, amphetamines, nicotine, ethanol
and cocaine all increase the release of dopamine in the nucleus
accumbens.
Cortex
MIDBRAIN
(A10)
M FB
Nucleus
accumbens
Amygdala