Basic Principles of Neuroscience PDF

Introduction to Neuroscience Dr James Bisby UCL Division of Psychiatry MSc Clinical Mental Health Sciences / Mental Health Sciences Research  What is neuroscience? Neuroscience is the study of the nervous system, not just the brain The most...

Introduction to Neuroscience Dr James Bisby UCL Division of Psychiatry MSc Clinical Mental Health Sciences / Mental Health Sciences Research  What is neuroscience? Neuroscience is the study of the nervous system, not just the brain The most fundamental division is between the – Central nervous system – Peripheral nervous system Central Nervous System  Peripheral Nervous System Somatic nervous system – receives and transmits information from the senses or to the muscles – Sensory nerves (sensation) – Motor nerves (muscle contraction) Via the spine (spinal nerves) or brainstem (cranial nerves)  Peripheral Nervous System Autonomic nervous system – maintains essential bodily functions largely without conscious control Breathing, pupil dilation, sexual arousal, swallowing, digestion etc Two parts: Sympathetic nervous system – fight or flight Parasympathetic – rest and digest  Neuron Fundamental unit of the nervous system Consists of Cell body (metabolism of the cell) Axon (typically myelin covered fibre through which electrical impulses are transmitted and converted into chemical signals) Dendrite (tree like fibres which receive neurotransmitters as communication from other cells) Neuron  Neuron Although all have the same basic components......there are many types of neuron through the nervous system, each of which is specialised for specific tasks Different kinds of neurons  Communication The electrical signal is called an action potential It propagates down the axon due to electrically charged particles called ions that flow through ion channels in the axon membrane Negative concentration gradient More positive ions outside than inside the cell More potassium (K+) inside the cell More sodium (NA+) outside the cell Negative concentration gradient More positive ions outside than inside the cell Resting membrane potential -70mV  At rest, voltage-gated sodium and potassium channels are closed Action potential is a temporary shift in the membrane potential (from negative to positive) Signals from other neurons allow positive ions to flow into the cell and depolarise the membrane  When one channel opens and allows positive ions in, it depolarises the surrounding axon Voltage-gated channels open and the change in membrane potential passes down the axon – an action potential  Communication between neurons When an action potential reaches the axon terminal it needs to pass on the signal to the next cell. Neurons communicate with each other via synapses – the place where the neurons meet Action potential triggers a release of neurotransmitters into the synaptic cleft  Communication between neurons Neurotransmitters are picked up by receptors which can affect the functioning of the receiving neuron Receptors are neurotransmitter specific and can only be activated by that neurotransmitter or a chemical which fully or partially mimics it  Synapse When postsynaptic receptors are activated they open ion channels to allow in specific ions Change the charge inside the receiving neuron and likelihood of a new action potential Free neurotransmitters in the synapse are either broken down by enzymes......or reabsorbed by the axon terminal by reuptake proteins  Drug Action This can explain how many drugs work at the level of cell biology Selective serotonin reuptake inhibitors (SSRIs like fluoxetine aka Prozac) prevent the reuptake of neurotransmitter serotonin......meaning more stays in the synaptic cleft so there is more free serotonin......and so serotonin receptors are more frequently activated  Drug Action Other drugs mimic neurotransmitters and trigger neurotransmitter specific receptors (called agonism) Some block receptors (called antagonism) Some act directly on ion channels Some affect the enzymes or proteins that ‘clear up’ free neurotransmitters etc  Drug Action Because of the different use of specific neurotransmitters and receptors in the brain’s systems...... to varying degrees drugs can selectively affect specific circuits, behaviours and perceptual systems  Many Biological Factors However, anything that can affect the function of the nervous system has the potential to affect us. Proteins are the ‘workhorses’ of biology and can be subject to many forms of change, alteration and dysfunction (e.g. in Alzheimer’s disease) Generation and regeneration of key cells (during neurodevelopment and through stem cell therapy) Virtually any aspect of cell metabolism  Many Biological Factors Larger scale aspects of the body’s metabolism and signalling can also have an impact on the nervous system in the short and long-term Oxygen Glucose Hormones Nutrients  Introduction to Neuroscience Part 2 Dr James Bisby UCL Division of Psychiatry MSc Clinical Mental Health Sciences / Mental Health Sciences Research Lobes  Neuroanatomy Grey matter (cell bodies – traditionally the brain’s “computation”) White matter (axons – traditionally the brain’s “cabling) Myelination of axons (fatty tissue) produces the white colour (multiple sclerosis due to damage to myelin)  Cortex Outer layers of grey matter in the brain Folded to allow for a large surface area More involved in higher cognitive functions related to deliberate action Microstructure (“cytoarchitecture”) varies across the brain Subcortical Structures White Matter Tracts (DTI image)  The brain is a network of networks Even if two brain areas are not directly connected through white matter tracts activity can be ‘passed on’ Meaning all brain areas can be functionally connected Something similar happens in cities e.g. although there is no direct transport link between Brixton and Barnet, you can travel between them  Network change Changes in structure and / or function of these networks are what determines how the brain learns, adapts and changes One key aspect is neuroplasticity  Neuroplasticity Many different types: Synaptic plasticity refers to changes in the strength of connections between synapses 1 – Increased NT release 2 – Increased NT binding 3 – Both alter the amount of ions entering the neuron and the electrical current to trigger an action potential  Neuroplasticity Synaptogenesis and synaptic pruning refers to the creation and removal of synapses  Neuroplasticity Neurogenesis is the creation of new neurons, a limited ability in the human brain. Neuronal migration is the process where neurons extend from their ‘place of birth’ to connect to far reaching areas across the brain. Neural cell death is where neurons die. Can happen through damage, over-excitation or disease, but also as a natural ‘programmed’ death called apoptosis.  Neuroplasticity Functional reorganisation is where functions of the brain are redistributed to other areas. For example, the primary visual cortex is active when blind people read Braille. Also, practice is associated with a reduction in brain activity and reduced distribution of brain activity over time  Neuroscience Methods Direct interventional studies typically alter something about brain function and examine the result For example, drugs, lesions, genetic changes or electrical stimulation Lesions and genetic changes may be introduced (animals) or studied in naturally occurring or secondary effect situations (humans with specific syndromes, after accidents or surgery)  Methods Measurements can involve direct examination of brain tissue, its functioning or metabolites (in vivo or post-mortem measures) Indirect examination of tissue, functioning or metabolites (neuroimaging) Testing behaviour, task performance, experience or association with other features (e.g. symptoms)  Introduction to Neuroscience Part 3 Dr James Bisby UCL Division of Psychiatry MSc Clinical Mental Health Sciences / Mental Health Sciences Research  How closely does cognition fit anatomy? Although you hear a lot of discussion about the ‘brain area for x’ (like the “hippocampus is the brain area for memory”)......this is misleading. Brain areas can be preferentially involved in certain functions but none are dedicated for specific functions.  Levels of Explanation It is often more helpful to think of different approaches – from the social to the biological – as using different levels of explanation. This also helps avoid the error of trying to classify disorders or problems as ‘social’ or ‘biological’ as if they were mutually exclusive Instead, we can think of social, psychological, cognitive, biological approaches as different tools for helping us understand the problem  Disciplines In practice, there is a great deal of overlap and there are many ‘neuro’ disciplines with slightly different emphasis but confusingly similar names. e.g. computational neuroscience, cognitive neuropsychiatry, neuropsychopharmacology, psychobiology, cognitive neuropsychology etc.  Neurobiology Deals with the nervous system and its interactions at the molecular and cellular level May be interested in understanding the complexities of Neuronal signalling Cell physiology Genetics and gene expression Interventions and pathologies (natural/artificial)  Three brainbows of mouse neurons (Lichtman and Sanes, 2008) The hippocampal dentate gyrus Purkinje cells in the cerebellum Mossy fibres (axons) of the cerebellum Axons of peripheral sensory neurons  Systems Neuroscience The study of neural networks From small groups of interconnected neurons to larger scale circuits in the brain Cortical column  Psychopharmacology Studies the neurobiology of substances that alter the mental state This can include medications (e.g. antipsychotics) common drugs (e.g. caffeine, nicotine) street drugs (MDMA, LSD) industrial chemicals (e.g. toluene) Dopamine receptor occupancy with different antipsychotics  Neuropsychology Looks at how the structure and function of the brain relates to how we think, feel and behave Based on standardised tests and experimental tasks that are known to reflect the function of specific brain mechanisms Typically conceptualises the brain’s work, cognition, as information processing Picture copies from patient with left-sided hemispatial neglect  Cognitive Neuroscience Looks at the neural correlates of thoughts, emotions and behaviour by measuring brain function Usually with neuroimaging but increasingly with interventions like transcranial magnetic stimulation or TMS Cortical activity during hand movement with fMRI  Computational Neuroscience Builds computer models of brain functions at various levels of abstraction to test ideas and theories Artificial neural network