Neuroanatomy + Neurochemistry Flashcards
Pupillary light reflex
Some light travels directly to pretectal area (not LGN), to Edinger-Westphal nuclei, which controls pupillary constriction via CN III.
Visual pathway
Optic nerve -> optic chiasm -> optic tract -> lateral geniculate nucleus (thalamus) -> visual cortex (posterior occipital lobe)
Basal ganglia - Components
= group of subcortical nuclei situated at base of forebrain and top of midbrain.
Components:
- Caudate + putamen (dorsal striatum)
- Nucleus accumbens + olfactory tubercle (ventral striatum)
- Globus pallidus
- Substantia nigra
- Subthalamic nucleus
Basal ganglia - Function
Associated with a number of functions including voluntary motor control, procedural learning, habit learning, conditional learning, eye movement, cognition, emotion.
The basal ganglia are inhibitory. They work with the cerebellum, which is excitatory, to allow smooth coordinated movement.
Basal ganglia - Neurotransmitters
Predominantly GABA-ergic efferent fibres, modulatory cholinergic fibres, and significant dopamine (in VTA and substantia nigra).
Nucleus accumbens
Component of the basal ganglia.
Involved in addiction.
Part of the reward pathway.
Hypothalamus - Function
Homeostasis
Hypothalamus - Inputs
- Nucleus of solitary tract (visceral sensation)
- Reticular formation (from spinal cord)
- Retina (from optic nerve)
- Circumventricular organs (monitor substances in blood)
- Limbic and olfactory systems
- Intrinsic receptors
Hypothalamus - Neural outputs
The lateral hypothalamus projects to lateral medulla, which contains cells involved in autonomic control. In this way, the hypothalamus can control HR, vasoconstriction, digestion, etc.
Hypothalamus - Endocrine outputs
- Large hypothalamic cells send axons directly to posterior pituitary, where they can release oxytocin and vasopressin directly.
- Smaller cells send axons to base of pituitary and release releasing factors into capillaries of anterior pituitary, which secretes hormones in response, such as TSH, ACTH, etc.
Orexin
Also called hypocretin.
Produced by lateral hypothalamus, but not during sleep.
Deficient in narcolepsy.
Medial preoptic nucleus
Part of hypothalamus.
Contains sexually dimorphic GnRH nucleus which releases gonadotrophic releasing hormone.
Supraoptic nucleus
Part of hypothalamus.
Releases oxytocin and vasopressin.
Paraventricular nucleus
Part of hypothalamus.
Releases oxytocin, vasopressin, and corticotrophin releasing hormone.
Anterior hypothalamic nucleus
Part of hypothalamus.
Involved in thermoregulation.
Suprachiasmatic nucleus.
Part of hypothalamus.
Involved in circadian rhythm (some fibres from optic nerve project here).
Releases vasopressin.
Ventromedial nucleus
Part of hypothalamus.
Involved in satiety, sexual behaviour.
Arcuate nucleus
Part of hypothalamus.
Involved in feeding.
Releases dopamine.
Lateral nucleus
Part of hypothalamus.
Involved in hunger, thirst.
Dorsomedial hypothalamic nucleus
Part of hypothalamus.
Involved in BP and HR.
Mammillary nuclei
Part of hypothalamus.
Act as a relay for impulses coming from the amygdala and hippocampus, via the mamillothalamic tract to the thalamus.
Therefore involved in memory.
Thalamus - Function
Regulation of sleep/wake
Processing/relaying of sensory information
Arousal/consciousness
Thalamus - Connections
- to the hippocampus via mammillothalamic tract (mammillary bodies and fornix)
- to cerebral cortex via thalamocortical tract
- from spinal cord via lateral and anterior spinothalamic tracts
Thalamic syndome
Contralateral hemi-anaesthesia + mood swings
Frontal lobe - Function
“Action cortex”
Involved in actions such as skeletal and ocular movement, speech control, expression of emotions.
The prefrontal cortex is involved in reasoning.
Orbitofrontal syndrome
Impulsivity, disinhibition.
Also called pseudo-psychopathy, Witzelsucht.
Mediofrontal syndrome
Apathy, akinetic mutism
Dorsolateral frontal syndrome
Impaired executive function
Tests of frontal lobe function
- finger tapping
- design or verbal fluency
- Wisconsin card sorting test
- tests of language, numeracy or decision making
- Stroop test
- Tower of London
- trail-kaing
Anterior cingulate
Part of frontal lobe
Involved in detection of errors, anticipation and preparation for tasks, emotion regulation.
Involved in mood disorders.
Broca’s area
Dominant inferior frontal cortex
Involved in generation of speech
Non-dominant dorsolateral/orbitofrontal cortex & insula
Depersonalisation
Temporal lobe - Function
Involved in processing sensory information.
- Visual memories (communicates to hippocampus, mediated by amygdala)
- Processing auditory (primary auditory cortex and superior temporal gyrus) and visual (ventral temporal cortex) input
- Language recognition
- New memories (hippocampi in medial temporal lobe)
Fusiform gyrus
Recognition of faces (prosopagnosia).
In temporal lobe.
Parahippocampal gyrus
Recognition of scenes
In temporal lobe
Wernicke’s area
In dominant temporal lobe
Brodmann area 22
Language comprehension
Mediobasal temporal lobe
Deja vu/jamais vu
Uncus
Olfactory hallucinations originate from here.
Common origin of temporal lobe epilepsy.
Lies next to the parahippocampal gyrus, which contains primary olfactory cortex.
Parietal lobe - Function
Integrates sensory information from various modalities (spatial sense, proprioception) and involved in language processing.
Functions include two-point discrimination, graphaesthesia, touch localisation.
Unilateral parietal lobe lesion
Contralateral hemianaesthesia
Agraphaesthesia
Contralateral homonymous hemianopia
Contralateral extinction phenomenon (unable to perceive one of two simultaneously presented stimuli in same sensory modality)
Sensory seizures
Lesion of dominant parietal lobe
Dysphasia/aphasia
Dyslexia
Apraxia
Gerstmann syndrome (agraphia, acalculia, left-right disorientation, finger agnosia)
Lesion of non-dominant parietal lobe
Spatial disorientation
Constructional apraxia
Dressing apraxia
Anosognosia (lack of insight)
Lesions of bilateral parietal lobes
Balint’s syndrome = simultanagnosia, optic ataxia, oculomotor ataxia
Lesion of unilateral occipital lobe
Homonymous hemianopia
Parieto-temporal-occipital association area
Lesion leads to colour agnosia, movement agnosia, agraphia.
Cerebellum - Function
Motor control, particularly coordination, precision, accurate timing.
Inferior olivary nucleus
In medulla
Coordinates signals from cerebellum to regulate coordination and learning
Receives inhibitory signals via GABA
Cerebellum - Tests
Gait (ataxia)
Finger-pointing
Dysdiadachokinesia
Subthalamic nucleus
Located at junction of midbrain and diencephlon
Functions as part of basal ganglia
Contains glutaminergic neurons which project to globus pallidus
Lesion leads to contralateral hemiballismus
Brainstem - Components
- Midbrain - includes substantia nigra, reticular formation (contains locus coeruleus), ventral tegmental area
- Pons
- Medulla
Ventral tegmental area
Located in midbrain
Projects throughout brain (mesocortical and mesolimbic pathways)
Part of reward pathway
Contains dopaminergic, GABAergic and glutamatergic neurons
Locus coeruleus
Located in reticular formation in midbrain
Involved in intensive alertness and autonomic reflexes
Contains noradrenergic neurons
Mesolimbic pathway
= the reward pathway.
Dopaminergic.
Connects the VTA (midbrain) to ventral striatum (basal ganglia).
Regulates incentive salience, facilitates reinforcement and reward-related motor function learning.
Clinical significance of Mesolimbic pathway
- Addiction
- Schizophrenia (increased dopamine in this pathway is linked to positive symptoms)
- Also implicated in depression and Parkinson’s
Mesocortical pathway
Dopaminergic pathway.
Connects VTA to prefrontal cortex:
- Ventromedial prefrontal cortex (mood)
- Dorsolateral prefrontal cortex (executive function and cognition)
Involved in cognitive control, motivation, emotional response.
Nigrostriatal pathway
Bilateral dopaminergic pathway.
Connects substantia nigra (midbrain) to dorsal striatum (caudate + putamen, in basal ganglia).
Part of the basal ganglia motor loop involved in production of movement.
Clinical significance of Nigrostriatal pathway
- Parkinson’s (degeneration of dopaminergic neurons in substantia nigra reduces dopamine function, with resulting motor deficits)
- Schizophrenia (presynaptic dopamine metabolism altered, antipsychotics can cause EPSE/parkinsonism)
Tuberoinfundibular pathway
Dopaminergic pathway.
Connects the arcuate nucleus (hypothalamus) to median eminence.
Dopamine released inhibits prolactin secretion, so antipsychotics which block this pathway will cause increased PL.
Neurotransmitters
Signaling molecules secreted by a neuron to affect another cell. Generally synthesised in neurons from precursor molecules. Released in response to action potential from synaptic vesicles into synaptic cleft, where they can interact with receptors on target cell.
Metabotropic receptor
G-protein-coupled receptor
Initiates a number of metabolic steps to modulate cell activity
Indirectly linked with ion channels through signal transduction molecules (such as G proteins)
Ionotropic receptor
Ligand-gated ion channels
Allow ions to pass through in response to neurotransmitter binding
Neuromediator
Also called second messenger.
Postsynaptic compound that participates in generation of postsynaptic responses.
For example; cGMP cAMP
Neurotrophin
Released by postsynaptic structures to maintain the presynaptic neuronal structure
Neuromodulator
Originate from non-synaptic sites
Influence neuronal activity
For example; steroid hormones
Neurohormone
Peptide secreted directly into bloodstream, that acts on other neurons
For example; pituitary hormones
Glutamate
- Most prevalent neurotransmitter
- Excitatory
- Amino acid
- Excessive glutamate release can cause overstimulation and excitotoxicity
- Metabotropic receptors: metabotropic glutamate receptors
- Ionotropic receptors: NMDA, kainate, AMPARs
GABA
- Second most prevalent neurotransmitter
- Inhibitory
- Amino acid
- Metabotropic receptors: GABA-B
- Ionotropic receptors: GABA-A, GABA-A-p
Acetylcholine
- Activates skeletal muscle, either excites or inhibits viscera in autonomic system, acts centrally in brain
- Metabotropic receptors: muscarinic ACh
- Ionotropic receptors: nicotinic ACh
- Primary source is nucleus basalis of Meynert (NBM)
Dopamine
- Monoamine
- Involved in regulation of motor behaviour, motivation/reward, emotional arousal
- Low in Parkinson’s, high in schizophrenia
- Metabotropic receptors: dopamine receptor, TAARI
Serotonin
- Monoamine
- 90% found in intestine in enterochromaffin cells, with remainder in CNS
- Involved in appetite, sleep, learning/memory, mood, behaviour
- Metabotropic receptors: 5-HT1, 2, 4, 5, 6, 7
- Ionotropic receptors: 5-HT3
Noradrenaline
- Monoamine
- Synthesised from tyrosine in CNS and sympathetic nerves
- Primary source is locus coeruleus
- Modulates autonomic nervous system, sleep patterns, alertness
- Metabotropic receptors: adrenergic receptors
Adrenaline
- Monoamine
- Synthesised from tyrosine, released in adrenal glands and brainstem
- Involved in sleep, alertness, fight-or-flight
- Metabotropic receptors: adrenergic receptors
Ghrelin
Neuropeptide
Produced in stomach
Promotes hunger
Leptin
Neuropeptide
Produced by adipose
Reduces hunger
BDNF
Neurotrophin
Helps support neuron survival and differentiation of new neurons/synapses
Decreased by stress
Increased by exercise, SSRIs
Neurotransmitter metabolism
First step usually hydroxylation.
This is followed by decarboxylation.
Feedback mechanisms to balance excitation and inhibition.
Dopamine metabolism
L-phenylalanine converted by phenylalanine hydroxylase to L-tyrosine, which is converted by tyrosine hydroxylase to L-dopa (rate limiting step), which is converted by dopa decarboxylase to dopamine.
Dopamine breakdown
Dopamine is converted to inactive metabolites by, MAO-A, MAO-B (inhibited by seligline) and COMT (note diGeorge syndrome). These are further broken down to metanephrines and normetanephrines by aldehyde dehyroxylase.
Dopamine is also converted by dopamine beta-hydroxylase to noradrenaline, which is converted by PNMT, with SAMe as co-factor, to adrenaline.
Glycine metabolism
Serine is converted to glycine (excitatory), by serine transhydroxymethylase, with pyridoxal phosphate as co-factor.
Glutamate/GABA metabolism
Glutamate is converted by glutamate decarboxylase to GABA, with pyridoxal phosphate as co-factor.
GABA is converted back to glutamate via GABA shunt pathway.
Serotonin metabolism
Ingestion of tryptophan is the rate-limited step. Tryptophan is converted by tryptophan hydroxylase to 5-HTP, which is converted by 5-HTP decarboxylase to serotonin. Serotonin is then converted by MAO-A to 5-HIAA.
[Note low MAO-A levels associated with conduct issues. Low 5-HIAA levels associated with aggression, eating disorders, suicide attempts.]
Basal ganglia pathology
- Huntington’s chorea (caudate nucleus)
- Wilson’s disease (copper deposition in putamen + globus pallidus (lenticular))
- Parkinson’s disease (substantia nigra)
- Hemiballism (subthalamic nucleus)
Caudate - blood supply
Anterior and middle cerebral arteries.
The symptoms and signs from caudate infarctions vary but behavioural symptoms, especially abulia and agitation, loss of executive abilities, and motor weakness are most common.
