Lecture Exam 3 Flashcards
Temporal Categories of Memory
Immediate memory
Short-term memory
Long-term memory
Forgetting
Immediate Memory
Fractions of a second-seconds
- The routine ability to hold ongoing experiences in mind for fractions of a second.
- The capacity of immediate memory is very large and each sensory modality (visual, verbal, tactile, and so on) appears to have its own memory register
- Example: While making saccadic eye movements, we are continuously getting new ‘snapshots’ of the visible environment.
- Example: Memory of somebody walking across the room just a second ago and knowing they moved to the right.
Short term memory
Seconds-minutes
- The ability to hold and manipulate information in mind for seconds to minutes while it is used to achieve a behavioral goal.
- Example: Searching for the ketchup bottle in the fridge, you know what you are looking for while looking around
- Asking somebody to repeat numbers 475 or use digit span testing (most people can remember approximately 7-9 digits)
Working memory
Seconds-minutes
- A part of short term memory but introduces a manipulation component.
- Example: Not only asking to repeat numbers 475 but to tell you them backwards.
Long term memory
Days-years
- Retaining information in a more permanent form of storage for days, weeks, or years.
- Important/significant information can enter long term memory (from immediate or short-term) by conscious or unconscious rehearsal or practice.
- Example: I remember my 8th birthday party, where you were on 9/11. Highlights importance of emotional salience which promotes consolidation.
Engram
- The physical embodiment of the long-term memory in neuronal machinery
- “Single memory unit”
- Depends on long-term changes in the efficacy of transmission of the relevant synaptic connections, and/or the actual growth and reording of such connections.
- Example: The memory is represented by protein changes, generation of new proteins or AMPA which will improve strength of synaptic connection; this may be where the memory actually can be.
- Example: We know if hippocampus is damaged you lose memory, so the theory is that they have to be localized somewhere.
Consolidation
- Aspect of long term memory which refers to the progressive stabilization of memories following initial encoding of memory “traces”.
- Requires changes in gene expression, protein synthesis and synaptic plasticity (e.g., AMPA cell phosphoralation)
Engram + Consolidation
Both of these topics are ‘controversial’. No evidence for a physical site of memory storage. Memory is not a one-size-fits-all situation.
2 Forms of Long term Memory
- Semantic/Declaritive/ EXPLICIT
- Skill learning/Nondeclaritive/IMPLICIT
Implicit Memory
Nondeclarative; unconscious recollection of previously learned information. This type of memory is typically manifested in an automatic manner, with little conscious effort of the subject.
-Examples: Priming, Procedural (skills and habits), Associative learning (classic and operant conditioning), Nonassociative learning (habituation and senstization).
Explicit Memory
Declarative; deliberate or conscious retrieval of previous experiences as well as conscious recall of factual knowledge about people, places, facts and events.
Examples: Facts (semantic) and Events (episodic).
Brain systems underlying declarative memory acquisition and storage
Reliant on midline diencephalic and medial temporal lobe structures. Hippocampus in particular.
- Papez/Limbic Circuit
- Prefrontal cortex, forebrain, fornix, thalamus, mamillary bodies, amygdala, rhinal cortex, hippocampus, MMT, corpus callosum, temporal lobe.
Posterior hippocampus and spatial navigation
Together with the entorhinal cortex, the hippocampus has specialized cells with receptive fields that specifically respond to spatial location.
Appreciate that there are cells in the posterior hippocampus that respond to SPATIAL LOCATION and have denser connectivity in this range
Example: study where taxi drivers have increased area of posterior hippocampus than controls.
Rodent models of spatial learning
“Place cells” which fire for being in a very specific location. Was proven with the morris water maze task for rodents.
Rats will learn where pedestal is in water to rest. If you remove the pedestal and everything else stays same “place cells” will activate and they will swim immediately to where platform is. If you damage hippocampus there is no memory for were that platform was.
(CA 1, CA2, CA3, DG, FI)
Patient HM (1926-2008)
- Seminal case for understanding why temporal lobe is important for memory.
- HM suffered from severe epilepsy.
- Dr Scoville, a neurosurgeon, localized the seizures to the R and L medial temporal lobes.
- Dr Scovelle actually removed more than just the hippocampus, HM ended up with a bilateral anterior hippocampal, amygdalar and entorhinal cortical resection.
- HM was mostly cured of his epilepsy by his surgery
- However, he suffered profound ANTEROGRADE AMNESIA. Inability to form new episodic memories.
- Brenda Milner discovered that his working memory and procedural memory were intact (examples: could do mirror drawing test, draw a path through a maze, tower of hanoi game)
Where memory likely is “stored”
Evidence for cerebral cortex as the major long-term repository for many aspects of declarative memory.
Association
- Important for storage
- Ability to remember meaningless information is extremely limited. Must ASSOCIATE things with something else or provide meaning/context.
- Mneumonists assign meaning to number strings to remember them beyond typical 7-9 digit span (Ex: Singling the digits of Pi decimels)
Association Research
- Research on depression indicates those with depression will attend to certain negative memories over good or have a different attending pattern. People who are depressed have rumination and bias to remember negative experiences over positive experiences.
- Storage of information is important for association based cues. For example, when HUNGRY subjects have increased ability to recognize a certain food item or non-food item. When people are SATED they recognize food or non-food items at similar level.
Conditioned learning
-Generation of a novel response elicited by repeatedly PAIRING a novel stimulus with a stimulus that normally elicits a response.
Classical conditioning
Conditioned learning.
Innate reflex is modified by associating normal trigger with an unrelated stimulus (e.g., Pavlovs dogs)
Amnesia
Abnormal forgetting or pathological forgetfullness
The inability to learn new information or to retrieve information that has already been acquired
Retrograde Amnesia
Difficulty retrieving memories established prior to precipitating neuropathology
- More typical of the generalized lesions associated with head trauma
- Also affected by neurodegenrative disorders, such as AD
- This tells us that while the hippocampus/midline diencephalic structures form and consolidate declarative memories, they are ultimately stored elsewhere
Anterograde Amnesia
An inability to establish new memories following neurological insult
Agnosia
Inability to recognize stimuli.
Often misinterpreted as memory deficit, but does not result from memory, attention, language problems or unfamiliarity to the stimuli.
Results from dysfunction of one of the sensory modalities: visual, tactile, auditory.
Visual example: when seeing cup, “its red, its smooth” verse when touching the cup “its a mug”
Prospagnosia
Inability to recognize faces .
Phonagnosia
Inability to recognize voices
Korsakoffs
Amnestic disorder caused by thiamine dieficiency associated with prolonged injestion of alcohol.
Mammillary bodies severely degenerated, part of circuit for forming memory
Major symptoms of alcoholic Korsakoff syndrome:
- Anterograde amnesia
- Retrograde amnesia
- amnesia of fixation (loss of immediate memory)
- confabulation
- minimal content in conversation
- lack of insight
- apathy
Example: Potential absence of certain vitamins in diet, B12+ or thiamine deficiency, you cannot produce enough energy for cells to work at level of mammillary bodies OR difficulty with kidneys where these nutrients are ultimately absorbed.
Korsakoff + Thiamine
Thiamine is essential for decarboxylation of pyruvate.
Deficiency during this metabolic process is thought to cause damage to the medial thalamus and mammillary bodies of the posterior hypothalamus as well as generalized cerebral atrophy.
These brain regions are all part of the limbic system, which is heavily involved in emotion and memory.
Anatomy of neocortex
Components of cortical structure 6 LAMINAE (counted from the surface of cortex inward toward white matter) 1. Molecular layer 2. Small pyramidal layer 3. Medium pyramidal layer 4. Granular layer 5. Large pyramidal layer 6. Polymorphic layer
Composition of…
- Molecular layer
- Small pyramidal layer
- Medium pyramidal layer
- Granular layer
- Large pyramidal layer
- Polymorphic layer
- Molecular layer is dendrites and axons
- Small pyramidal layer made of pyramidal cells. Foster cortico-cortical connections (between lobes, areas)
- Medium pyramidal layer made of pyramidal cells and local-axon collaterals. Foster cortico-cortical connections (between lobes, areas)
- Granular layer made of stellate cells and THALAMIC in nature
- Large pyramidal layer made of dendrites and SUBCORTICAL (besides thalamus)
- Polymorphic layer made of descending axons and deep white matter with OUTPUTS TO THALAMUS
Cerebral localization and key principles
Explanations for function:
Localized processes vs distributed networks.
Explanations for dysfunction:
Localized lesions, false localizations, disconnections
Critical principles
1) Anatomic distinctions apply functional distinctions.
2) . Localized damage can have systemic effects
Example: Lesions in one area (occipital lobe or association areas) may have extending consequences as they are not “localized” to the occipital lobe because of vast connections to other regions of cortex.
3) Patterns of connectivity important. Some syndromes reflect loss of processors others reflect disconnection.
Example: If lesion in white matter connection between language and vision regions –> impairs reading ability.
Hemispheric Lateralization
95% R handed language dominance on L side
5% L handed language dominance on R side
Left Dominant Hemisphere
- Complex motor processes
- Language
- Verbal memory
- Arithmetic: sequential and analytical calculating skills
- Musical ability: sequential and analytic skills in trained musicians
- Sense of direction: following a set of written directions in a sequence
Overall, language, sequencing, calculating, complex motor. Think renaissance man/woman who is verbally eloquent, plays piano also does science/math.
Right Non-Dominant Hemisphere
- Gestalt (many things in a scene)
- Visiospatial skills
- Attention to environment (attention to L and R visual fields)
- Arithmetic (estimation, line up columns)
- Emotional significance to events and languae
- Musical ability in untrained musicians
- Sense of direction (spatial orientation)
Overall, intonation, visuospatial skills and attention. Think boat captain on open waters messing around with guitar. Needs basic calculation skills but really good sense of navigation.
Dorsal Stream
Tells us the “where and how”.
Terminates in parietal association cortex.
Functions to incorporate data from other cortical regions with visual information (proprioception, vestibular, auditory).
Key features:
- processes motion
- active for manipulable objects
- integrates spatial location
Dorsal Stream Damage
R hemisphere dorsal pathway lesion causes severe left neglect.
L hemisphere dorsal pathway lesion causes minimal right neglect.
Partial bilateral lesions to both dorsal pathways cause sauvere R neglect.
Hemispatial Neglect
Secondary to lesions of parietal association areas.
Typically, neglect for contralesional LEFT side of space secondary to RIGHT parietal damage.
In health, R parietal cortex attends to L and R visual field while L parietal only attends to R visual field. Therefore, a lesion in R the left cortex only attends to the R visual field so there is no attention from the R cortex to see the L visual field.
Bias to R side of scene, even if the entire scene is within the “central” visual field
Extinction: Only see left side of “central scene” wen right side is hidden/removed.
Sensory hemispatial neglect
Sensory (visual, tactile, auditory): Will ignore visual, tactile or auditory stimulation in contralateral hemispace, even though sensation is intact.
Action/intentional hemispatial neglect
Will perform fewer movements in contralateral hemispace
Egocentric hemispatial neglect
Profound neglect for the contralateral half of the external world and own bodies.
Simultanagnosia
Parietal/dorsal stream deficit.
Impaired ability to perceive parts of visual scene as a whole.
Deficit in visuo-spatial blidning.
Optic ataxia
Parietal/dorsal stream deficit.
Impaired ability to reach for something under visual guidance
Ocular aprxia
Parietal/dorsal stream deficit.
Difficulty voluntarily directing gaze to periphery
Bilants syndrome
Parietal/dorsal stream deficit.
Triad of optic ataxia, ocular apraxia and simultanagnosia.
Bilateral dorsalateral parieto-occipital association cortex lesions.
Often caused by MCA-PCA watershed infarct.
Gerstmann’s Syndrome
Localized to dominant inferor parietal lobe deficit at angular and supramarginal gyrus.
Includes agraphia (cant write), acalculia (cant do simple math), finger agnosia and left-right confusion
Ventral stream
Tells us the “what”
Moves across the temporal lobe. Posterior temporal lobe giving us simple imagery and graduating to more complex/3D images at anterior temporal lobe.
Right ventral stream…
Also gives information on range of rhythm, intonation, pitch, rate, and intensity used to convey meaning in language. There are both receptive and expressive prosody.
Right ventral stream
Affective prosody: emotional state
Linguistic prosody: sentence meaning (rising intonation with a question )
Expressive prosody: production
Receptive prosody: comprehending others production
Aprosodia
Lesion to R temporal association area.
Condition in which a person loses their ability to convey or interpret linguistic prosody.
Caused by damage to R hemisphere brain regions homologues to L hemisphere brain regions responsible for language production or reception.
However, literature is mixed because damage to other brain regions can cause this (frontal lobes), and emotional language is distributed throughout the brain.
Agnosia
Lesion to R or L temporal association areal.
Gnosis = knowledge; A = without –> failure to recognize previously familiar stimula
Modality specific (visual, auditory, tactile)
Visual agnosia more common due to bilateral PCA stroke.
May be limited to a particular class of stimuli (e.g., living things, medical equipment) .
Apperceptive Agnosia
Apperceptive agnosia: primary sensory defect (unable to copy or ID)
If visual in visual association cortex (occipital)
If auditory lesion in auditory association cortex (temporal)(
Associative Agnosia
Associative Agnosia: primary problems with identification. Can copy and perceive.
Disconnects sensory cortices from semantic areas.
Typically associated with anterior temporal damage.
Apperceptive vs Associate Agnosia
Apperceptive there is a problem with perceiving the object
Associative you can perceive it, but you cannot associate it. Patients can copy it fine but cant tell you what it is.
Propopagnosia
Lesions to bilateral inferior occipital-temporal cortex (fusiform gyrus) or junction of visual association cortex and temporal lobe. May be congenital .
Inability to recognize faces.
CANNOT: ID individuals, recognize a face, describe the owner of the face, feel familiarity when viewing faces.
Interpreted as intact “generic” recognition with impaired “specific” recognition.
Achromatopsia
Due to V4 lesions or parieto-temporal-occipital cortex.
Cortical color blindness
Can affect quadrant, hemifeld or entire visual field
Colors appear to be in shades of gray
Cannot name, point to or match colors.
Can name colors presented verbally: what color is grasss? green.
Color agnosia
Inability to name “red items” (e.g., strawberry, apple, heart, etc.)
YET can match/differentiate colors when asked.
Akinestopsia
Lesions to V5 or mesio superior temporal area.
Inability to perceive motion, “motion blindness” .
Depending on severity, may see movement as stroboscopic or may not perceive any motion.
Very dangerous functionally. Cannot perceive cars moving.
YET normal spatial acuity, flicker detection, color vision.
Functional specialization of association cortices
Occipitotemporal = pattern/object recognition, color
Parietal = spatial, action/motor, attention
Dorsal (occipito-parietal) Stream
R side damage
Hemineglect to L Simultanagnosia Optic ataxia Ocular apraxia Balints syndrome
Dorsal (occipito-parietal) Stream
L side damage
Agraphia
Acalculia
Finger agnosia
L/R confusion
Ventral (occipito-temporal) Stream
R side damage
Aprosodia
Ventral (occipito-temporal) Stream
L side damage
Agnosia (apperceptive or associative) Prosopagnosia Achromatopsia Color agnosia Akinetopsia
Emotion
No consensus on definitionbut involves 3 key components:
1) Cognitive appraisal
2) Feeling (subjective changes)
3) Action
Reaction to some stimulus that has an effect internally or externally
“An inferred complex sequence of reactions to a stimulus including cognitive evaluations, subjective changes, autonomic and neural arousal, impulses to action, and behavior designed to have an effect upon the stimulus that initiated the complex sequence (i.e., it’s functional).” (Plutchik, 1982)
Ekaman’s emotion research
Basic emotions exist secondary to universal facial expressions.
Pioneered research using facial expressions in cultures across the world and boiled it down to 6 universally recognized emotions.
Joy, contempt, suprise, sadness, anger, disgust, fear
Yet, others propose 7 or more.
Componential Approach
Ortony & Turner
Emotions are not basic. Instead, elementary INDEPENDENT components of visceral-autonomic emotions are innate. We learn to construct emotions using components in early social development. The components aren’t bound together internally.
A lot of evidence that emotions are not basic; atomizing of emotions as a mixture of independent components.
Ex: ANGER 1) furrow brow 2) . open teeth 3) compress lips
Social Constructivism
J. Averill
Emotions are social constructs, not basic nor universal. Emotions depend on SOCIETY we are in.
Different societies have untranslatable emotional vocabularies and therefore fillings.
Emotion research is theoretically flawed (lab conditions, cultural differences, lack of familiarity, conflicting variables)
James Lang Theory
Emotion is a response to physiological change in the body (we cry and then feel sad, we smile and then feel happy)
Stimulus –> Reaction –> Emotion
Cannon-bard theory
Emotions are indepent of emotional expression.
Physiological arousal does not always = emotion.
Emotional experience and physiological arousal occur separately and usually simultaneously.
Stimulus -> Emotion -> Reaction
Schachter and Singers Two Factor Theory
Merges Cannon-bard and James-lang.
Physiological arousal can lead to emotion but cognitive appraisal is important.
Same physiological arousal for multiple emotions.
Example: Your heart rate is elevated, your breathing is fast and you feel jittery. Anxiety from test taking or too much coffee or watching an exciting game?
Dimensional Approach
Emotions are organized along three independent dimensions.
Valence (positive/pleasant to negative/unpleasant)
Arousal (low to high)
Movement/Action (movement toward vs movement away) like fight or flight
Quantifying emotions
3 broad response systems
1) Verbal report (mood, subjective interpretation, expression/prosody, discourse analysis)
2) Behavior (facial, face digitizing, electromyogram, MDVP, gestures, whole body)
3) Physiologic activation/arousal (skin conductance/pupils); Central(EEG, startle response, FMRI,PET); Pyschological factors affecting medical condition
The limbic lobe
Cortex forming a ring around corpus callosum. Cingulate gyrus, medial temporal lobe, hippocampus.
The Papez Circuit
Limbic System Concept
Limbic structures including cortex are involved in emotion
Emotional system on the medial wall of the brain linking cortex with thalamus
Evolution of limbic system allows animals to experience and express emotions byond stereotyped brainstem behaviors (simple reactions)
The Papez Circuit
Localizations and Function
Cortex (emotional experience)
Hippocampus (mediates behavioral expression of emotion. example, hyperemotional response secondary to hippocampus changes in patients with rabies)
Anterior thalamus (lesions lead to PBA)
Amygdala: fear, anxiety, apprehension, defensive motivation
Amygdala + Emotion
Connects diffusely throughout brain. BG, cerebellum, thalamus, frontal, brainstem, etc.
Amygdala + Fear
Bilateral amygdalectomy reduces fear and aggression in all animals tested.
Anger, sadness, and disgust may be effected
Electrical stimulation of amygdala -> increased vigilance or attention. Seizures with temporal lobe foci can have fear and panic as auros.
Fearful faces produce greater amygala activity than happy/neutral faces.
SM Case Study
Bilateral amygdal deconstruction.
Inability to recognize fear in facial expressions.
Little experience of negative emotions and much experience of positive emotions.
Little to no personal space.
Learned Fear
Amygdala involved in classic pavlovian responses; can condition fear.
Amygdala involved in fomring memories of emotional events (not just negative ones)
Confirmed by fMRI images and PET
Amygdala and Aggression
Predatory Agression - Attacks -Against different species for food -Few vocalizations; attack head or neck -No activity in sympathetic division of ANS -Medial Ex: Animal stalking pray
Affective aggression - For Show
-Used for show, not kill for food
-High levels of sympathetic activity
-Makes vocalizations; threatening posture
-Central
Ex: Football players threatening one another animalistically before game.
Surgery to reduce Aggession
Amygdaletomy
Psychosurgery (lobotomy) - last resort
Outcomes:
Reduced agressive social behavior
Increased ability to concentrate
Decreased hyperactivity
Temporal Lobectomy: Animals vs Humans
Temporal lobectomy in rhesus monkeys leads to decreased fear and aggression, decreased vocalizations and facial expressions.
Temporal lobectomy in humans (secondary to encephalitis, stroke, Co2 poisining, dementia) leads to symptoms of Kluver Bucy syndrome. Likely related to destruction of amygdala
Kluver Bucy Syndrome
Hyperorality, compulsive eating, hypersexuality, visual agnosia, docility/flattened emotions.
Ventral striatum (Nucleus Accumbens) + Emotion
Involved in pleasure, euphoria, reward circuitry.
Reward center of brain. Things we find enjoyable and all the surrounding emotions go through NA.
Stimulation of NA during DBS surgery for OCD treatment associated with laughter, smiling and intense feelings of pleasure/euphoria.
Septal Regions + Emotion
In basal forebrain you have septal nuclei. If you have lesion in this part of brain you wind up with aggression, rage. If this region is stimulated you get reward-seeking behavior.
Caveats with the Limbic System Concept
Difficulties with the single emotion system concept (in other words - the brain is not simple)
- Diverse emotions (many and mixed)
- Many structures involved in emotion (not 1:1 relationship between structure and function)
- Utility of a single, discrete emotion network (i.e., limbic system) is questionable
Brain structures mediating emotion
limbic system including limbic cortex and amygdala
Hypothalamus
Brainstem
Hypothalamus + Emotion
Deep brain structure made up of a number of nuclei (19 million neurons, 1/7th of a teaspoon)
Hypothalmus is located in base of forebrain, behind optic chiasm, forms part of the walls of 3rd ventricle, continous with infindibulum
Integrates emotional resposnes from forebrain, brainstem, spinal cord.
Sexual responses
Endocrine responses (neurosecretory, oxytocin, vasopressin)
Ablation Studies of Hypothalmus
Give evidence for role of hypothalmus in integrating emotions/behaviors.
In cats if you remove cortex and leave hypothalmus there is rage.
In cats if you remove hemispheres and hypothalamus, no rage.
The Hypothalmus and Aggression
Flynn 1960
Predatory (goal-oriented) agression elicited by stimulating LATERAL hypothalmus.
Elicited affective (reactive/hostile) agression by stimulation to MEDIAL hypothalamus
Neural components of agression beyond the amygdala
Periaquiductal gray (pain and agression), OFC, prefrontal cortex, hypothalmus, cingulate cortex.
Hypothalamus: Routes of information
Input from broad cortex (relatively unprocessed) straight to cortex and significant output to brainstem.
Brainstem + Emotion + Serotonin
Neurotransmitter serotonin.
Sertonergic raphe neurons in brainstem project to the hypothalmus and limbic structures via the medial forebrain bundle. Then spread diffusely throughout cortex.
Rx Example: Drug PCPA blocks serotonin synthesis results in increased aggression. Used to treat depression.
Example: Decreased serotonin turn-over (metabolism) results in increased aggression in rodents.
Cortex + Emotions
Cortex plays role in emotion regulation, interpretation and expression of emotional signals (facial expression, gestures, semantics, prosody)
Insula + Emotions
Insula particularly involved in emotion of disgust.
Connects to much of the rest of the brain. Plays significant role in emotional awareness (“feeling” emotion) and pain regulation.
Orbitofrontal damage + Emotion
Orbitofrontal damage and dysregulation often interpreted as personality changes.
Involved with impulsivity, irritability, disinhibition, overly friendly behavior, hypersexuality, risk taking, emotional lability, mood changes (depression and mania)
Medial frontal/AAC damage + Emotion
Medial frontal/AAC damage and dysregulation associated with poor motivation, flattened emotions, poor initiative, apathy, slowed behavior and thought.
Dorsolateral prefrontal damage + Emotion
Dorsolateral prefrontal damage/dysregulation associated with executive function deficits that can influence emotion regulation and judgement.
3 General Hypotheses for Emotion and teh Brain
1) R hemisphere is dominant for emotion
2) R hemisphere is automatic as compared to controlled L hemisphere
3) Laterality for mood exists. Positive/approach in left hemisphere with negative/withdrawal in right hemisphere.
Localized “Damage” and Emotion
Awakening from WADA procedure to right side results in crying/anxiety and left side results in laughing/excitement.
Acute stroke to RH results in indifference, mania.
Acute stroke LH results in depression.
Dorsalateral Prefrontal Cortex
Region + Connectivity
Region: Most frontal (in front of FEF and edge of frontal pole)
DLPFC --> Head of caudate --> GPi/SNr, GPe, STN --> VA, dorsomedial thalamus --> and back up to DLPFUC
Dorsalateral Prefrontal Cortex
Function
- Plan, problem solve, organize
- Response selection inhibition
- Working memory with executive function
Does this based on external criteria (ex: seeing dishes in sink, prompts you to wash them or organize time to)
Dorsalateral Prefrontal Cortex
Lesions
Decreased word fluency
Increased perservation (conversation or activities)
Increased need for compensatory strategies (cues to wash dishes)
Think patients with MTBI
Dorsalateral Prefrontal Cortex
Dx Testing
WI Card sorting task (problem solving, selection)
Stroop effect (learning one rule, then shifting to learn new rule. Example, say the color of the font but not to read the word, then do the opposite) tests working memory
MoCA tasks (clock drawing, memory, word fluency, etc)
N-Back (working memory)
Orbitofrontal Prefrontal Cortex
Region + Connectivity
Region: Brain area above where eyes typically are, inferior aspect of frontal lobe.
2 circuits, both receive external input from amygdala.
OFC lateral --> VM caudate --> GPi /SNr --> Va thalamus --> and back up to OFC lateral
OFC medial --> ventral striatum --> GPi /SNr --> Va thalamus --> and back up to OFC medial
Orbitofrontal Prefrontal Cortex
Function
- Determines personality
- Regulates social appropriateness
- Inhibits or facilites living with your ID
- Reward/emotional value
- Planning re: intrinsic factors
Orbitofrontal Prefrontal Cortex
Lesions
Decreased cognitive appraisal of all factors (social appropriateness, inhibition/facilitation of id, reward/emotional value, etc.)
Emotional lability
Decreased self awareness
Think RHD patient.
Orbitofrontal Prefrontal Cortex
Dx Tests
Iowa Gambling Task for emotional decision-making + impulsivity
bad cards (high money at first but end up losing more)
good cards (low money at first but end up gaining greater net)
Medial-Cingulate Prefrontal Cortex
Region + Connectivity
Region: located dorsal aspect of frontal lobe, directly above corpus callosum and cingulum.
MC PFC --> Ventral Striatum + NA + olfactory bulb --> RM GPi/ RD SN --> DM thalamus --> and back up to MC PFC
Note it communicates with premotor, motor areas and BG
Medial-Cingulate Prefrontal Cortex
Function
- Motivation to start and sustain both complex movement and goal directed behavior.
- Expression of emotion
- Conflict/resolution skills
Medial-Cingulate Prefrontal Cortex
Lesions
Akinesia of movement
Akinetic mutism
Apathy
Decreased self-initiated action
Think PD patients
Medial-Cingulate Prefrontal Cortex
Dx Tests
Apathy scale
Caregiver/Patient reports
General Circuit of Frontal Cortices
Cortex (frontal) ->
Striatum (caudate/putamen) ->
Pallidum (GPi/SN)->
Thalamus (VA or DM) ->
“Terminating” Nuclei of Frontal Cortices
Medial cingulate goes to DM thalamus
Dorsalateral and Orbitofrontal goes to VA of thalamus
Addiction
The term is antiquated. Better term is SUBSTANCE USE DISORDER.
It is the persistent and compulsive seeking and using of an intoxicating substance despite negative consequences on health, social, and/or occupational function.
Dopamine Studies
Dopamine Research has revealed that…
1) Drugs of abuse induce accumbens dopamine release
2) . Drug self-administration into accumbens and VTA observed
3) . Drug self-administration blocked by accumbens dopamine blockade
BUT - dopamine may be more important for “wanting” rewards than “liking” them.
Drugs of abuse + Dopamine
Is it based on reward? OR motivation for the reward?
Ex: Rats “enjoy” cocaine and are motivated/want it because the DA receptors or NA are active and sensitive massive DA input (coming from SN and VTA). BUT when those DA receptors are blocked, rats still enjoy cocaine but no longer have the drive to want it and will not have the signs of motivation to find/get cocaine in the future.
Hard to functionally/clinically parse out bc wanting and motivation often go hand in hand; can only do this in controlled lab settings.
NA Shell
NA shell associated with drug hedonics - also opiod and cannabanoid signaling.
Receives signals from VM PFC.
NA Core
NA core has influence on drug-predictive cues.
Receives signals from all areas of PFC (VM PFC, OFC, dACC, DPFC)
Amygdala + NA
Amygdala communicates with NA core, also influencing drug-predictive cues.
Feedback to Frontal Cortex + Addiction
Facilitates the behavioral output, encompasses all systems
Habenula
The “anti-reward” system that communicates with the RMTG, which inhibits SN & VTA centers of dopaminergic production
Habenula + Stimulant use
Habenula communicates with RMTg via fasciculus retroflexes. These communication fibers are damaged by stimulant use. Thus thwarting Habenula input.
Prefrontal Cortex Activity in Substance Abuse
Glucose metabolism of ORBITOFRONTAL CORTEX is significantly reduced in cocaine abuser as compared to controls.
This could theoretically be the consequence and/or cause of substance use?
What came first, chicken or egg?
Cortical & Subcortical Regions Involved in addiction
Medial prefrontal cortex (mPFC) Orbitofrontal cortex (OFC) Dorsal and ventral striatum Globus pallidus Thalamus Amygdala HIppocampus Nucleus accumbens shell and core Ventral tegmental area
Dopamine + Drug Seeking Behavior
DA releases signals to the brain that it should want to find the drug or behavior. The motivation is the drive for the behavior to use the substance.
Drugs of abuse hijack the dopamine system, telling the brain that “this is something I should want”
Drugs hijack the biological system of motivation for reward, like foraging for food, finding food, and being motivated to find it again if it was enjoyed.
Addiction Circuit:
Midbrain and NA
SNc and VTA release DA to NA shell (which is also sensitive to opiod and cannabinoid signals)
Addiction Circuit:
Hypothalamus/Brainstem and NA
NA shell sends projections to hypothalamus and brainstem.
Hypothalamus for autonomic/down regulation + increasing sympathetic system
Brainstem for increases of HR, BP, temperature
Addiction Circuit:
SNc & VTA + NA Core + Amygdala
SNc & VTA also send DA projections to NA core.
Amygdala also sends projections to NA core.
The NA core influences drug-predictive cues (like a bar for recovering alcoholic; or white powder on mirror).
Amygdala adds role in the “memories” of past experiences with the substance and emotionally salient information about stimulus to NA core.
Addiction Circuit:
NA shell + NA core + Ventral pallidum + Frontal Cortex
The shell and core provide GABA-ergic projections to ventral pallidum (bottom of GPi and GPe) which inhibits GP.
Therefore, thalamus is released from inhibition and sends GLUTAMATERGIC signals to the frontal cortex.
Thus, planning and premotor signals are excited, which act upon the motivation to the substance.
Addiction Circuit:
Habenula + RMTg
Of course, there is an antignositic or “checks/balances
system for this mechanism involving the HABENULA (also known as epithalamus). It is the anti-reward system.
It projects glutamatergic neurons to the rostral medial tegmental region RMTg.
When RMTg is excited, it releases gaba onto SNc and VTA.
This puts “brakes” on DA output to NA.
Theory that drug use degrades fasciculus retroflexus or connections between Habenula and RMTg.
Addiction Circuit:
Prefrontal Cortex + Amygdala
ONE MORE CIRCUIT…
Output from PFC projects back down to amygdala (which can affect hypothalamus, brainstem and NA core).
This is clinically significant because PFC is likely impaired from chronic substance use.
Therefore, it cannot influence or have a descending input on the NA to modulate the DA release.
PFC is important to plan and facilitate recovery, but this will be difficult if it is impaired.
Tx of Drug Addiction
There is hope. One study examined post-stroke smoking and noted that with insular infarcts patients just “stopped” smoking and claimed their bodies just forgot they needed nicotine.
Possible utility of “brain games”, however this seems to improve planning and executive function but not to decrease substance use.
Draw the Addiction Circuit
Draw
Draw the Limbic Circuit
Hippocampus Fornix Mammilary bodies MMT Anterior nucleus of thalamus Cingulate gyrus (through anterior limb of IC) Cingulum Hippocampus
Eye structure:
Optic nerve vascular supply
Supplied by central retina artery and vein
Eye structure:
Layers @ Posterior Segment
Retina
Choroid
Sclera (runs continuous with cornea)
Eye structure:
Ora Serrata
Division where retina at posterior segment ends and ciliary bodies of anterior segment begins.
Eye structure:
Ciliary body
Connects the iris to the choroid
Eye structure:
Ciliary muscle
Changes the shape of the lens (accomodation reflex)
Eye structure:
CIliary Zonular Fibers
For distance vision, ciliarus relaxes, zonular fibers tighten to FLATTEN central portion of the lens. INCREASED DIAMETER. Results in decrease in refractive power of the lens.
For close vision, ciliarus contracts, zonular fibers loosen and lens BULDGES. REDUCED diameter. Results in increase in convexity and refractive power of lens.
Eye structure:
Iris
Iris
Dilator pupillae (sympaethetic; dilates pupil)
Sphincter pupillae (parasympathetic; constricts pupil)
Eye structure:
Aqueous humor
Nourishes eye.
Keeps intraocular pressure at 10-20 mm Hg.
Secreted by ciliary processes in anterior segment –> posterior chamber –> pupil –> anterior chamber –> exits through schlemms canal
Eye structure:
Vitreous humor
Gel-like substance, fills middle eye, holds retina together.
TRANSMITS light rays to retina.
Maintains intraocular pressure during movement.
Eye structure:
Pupil
Hole that directs light to retina
Eye structure:
Choroid
Vascular layer of eye
Eye structure:
Retina
Photoreceptors lining back of eye.
Eye structure:
Macula
Small area at center of retina, for details (faces, texts).
Eye structure:
Fovea
Central depression of macula where eyesight is the sharpest
Eye structure:
Conjunctiva
Clear covering of white part of eye.
Eye structure:
Cornea
Clear dome-shaped covering to where light is directed.
Eye structure:
Lens
Focuses light back to eye. Changes shape for focus.
Retinal Structure:
Molecular Order
Inside –> Out
Pigmented epithelium RODS CONES (Outer nuclear layer) (Outer plexiform layer) (Start of inner nuclear layer) HORIZONTAL CELLS (GABAergic) BIPOLAR CELLS AMACRINE CELLS (End of inner nuclear layer) (Inner plexiform layer) GANGLION CELLS GANGLION AXONS
Retinal Structure:
Molecular Order
Inner nuclear layer
Horizontal cells
Bipolar cells
Amacrine cells
All interneurons
Release graded receptor potentials
Ultimate releases tiny bit of glutamate into inner plexiform layer
Retinal Structure:
Molecular Order
Inner plexiform layer
Ganglion cells
Ganglion axons
Level of SYNAPTIC CONNECTIONS which are stimulated by small amount of glutamate and ultimately facilitate action potentials.
RODS
Rods > Cones Rods dominate peripheral retina 1 pigment (gray scale / no color ID) Dark adapting (so we need a lot!)
RhodOPSIN
“11-cis retinal” / Vit A
CONES
Not distributed evenly
More concentrated twoard fovea
Increase edge detection
Increase visual acuity with bright light
Detects wavelegnths for color vision (R, B, G) –> thats why in fovea
3 pigments
PhotOPSIN picks up wavelengths of color
“11 cis-retinal” / Vit A
Rods + Cones Transduction
The same!
Draw phototransduction cascade.
Trichromatic Vision
Each visual pigment protein has a sequence for a particular wavelength (interpreted by 11-cis retinal)
Blue (S) - 450 lambda
Green (M) - 500 lambda
Red (L) - >650 lambda
Dichromatic Vision
Defect in one core color group is dichomatric vision
Tritanopia
Loss of S pigment –> Blue Color
Defect of chromosome 7
Deuteranopia
Loss of M pigment –> Green color
Defect of sex linked X chromosome
Proatnopia
Loss of L pigment –> Red color
Defect of sex linked X chromosome
Protanomoly/dueteronamoly
Mild color blindness
Point mutation of protein
Eye Arteries/Veins/Sinus:
Arteries
Branch of the internal carotid artery called the OPTHALMIC ARTERY
OPTHALMIC ARTERY is divides into two key branches. Central retinal artery and posterior ciliary arteries.
Central retinal artery supplies the retina.
Posterior ciliary arteries supplies choroid.
Eye Arteries/Veins/Sinus:
Damage to central retinal artery
Damage here can lead to blindness
Amaurosis fugax:
transient clot which leads to transient superficial blindenss secondary to DORSAL BRANCH TIA of CRA.
Often “warning” sign before more severe deficits.
Eye Arteries/Veins/Sinus:
Veins
2 key veins:
Superior opthalmic
Inferior opthalmic
both drain into cavernous sinus.
Eye Arteries/Veins/Sinus:
Cavernous sinus
Receives waste from superior opthalmic and inferior opthalmic veins.
Important as it houses CN 3, 4, 5, and 6!
Eye Arteries/Veins/Sinus:
Cavernous sinus damage
CAVERNOUS SINUS THROMBOSIS impairs vein drainage from eye and can result in proptosis (buldging) of the eye and can become bilateral.
Other deficits that can occur from venous congestion:
Pappiledema (swelling of optic nerve toward you secondary to increased intracranial or cavernous sinus pressure)
Retinal hemorrhages
Decreased visual acuity
Blindness
Optic Disk
A unique pressure sensor. A diagnostic ocular landmark allowing detection of intracranial abnormalities and glaucoma.
Physical changes underlying papilledema
Tumors, hematoma, block of CSF flow result in cupping of optic disk. Image of vasculature is TOWARD you.
Glaucoma
is NOT pappiledema (extraocular pressure). Image of vasculature is AWAY from you.
2 types
open angle
closed angle
Open Angle Glaucoma
One of major causes of blindness in adults in USA
Can loose peripheral vision
Increased ocular pressure in the absence of physical obstruction
Often secondary to increased pressure on axons of CN 2 or increased aqueous humor (rate or exit defect)
Goals of Rx: reduce amount o acqueous humor, reduce rate production of acqueous humor, increase outflow of humor
NOTE: Meds very effective for this but patients often don’t notice peripheral deficits or compensate for them simply by looking/moving head around more in setting of peripheral loss.
Close Angle Glaucoma
Can cause blindness.
Secondary to physical abnormalities; iris displaced forward, blocking chamber angle, adhesion between lens and iris.
Often due to trauma.
Dx of Glaucoma
Dilated eye exa: s/s of retinal vascular changes?
Visual field test: loss of peripheral vision?
Tonometry: pressure inside eye elevated?
Gonioscopy: evidence that anterior chamber angle is obstructed?
Presbyopia
Decreased elasticity of aging lens capsule resulting in reduced curvature of relaxed lens- difficulty focusing on near objects.
Pupillary Reflex Responses
Size of pupil reflects balance of parasympathetic and sympathetic drive.
In normal; DIRECT AND CONSENSUAL pupillary constriction responses.
Eye stimulated working - DIRECT response
Indirect and unstimulated eye responds - CONSENSUAL response
Pupillary Reflex Responses
Sympathetic vs. Parasympathetic
Sphincter pupillae muscle contraction decreases pupil size (parasympathetic)
Dilator pupillae muscle contraction increases pupil size (sympathetic)
Parasympathetic Puppiloconstrictor Pathway
Preganglionic parasympathetic part of CN 3 runs along outer portion of CN 3 --> EW --> brachium of superior colliculus --> Pretectal nucleus
Sympathetic Pupillodilator pathway
DESCENDING SYMPATHETIC PATHWAY
Autonomic regulatory nuclei from hypothalamus –>
superior cervical sympathetic ganglion in paravertebral sympathetic chain (CILIOOSPINAL CENTERS C8-T2) via IML–>
short ciliary nerve –>
iris dilator muscle
Eyes very dilated: could be damage to IML C8-T2 or descending sympaehtic pathway at 10/12.
Pupillary Response for Severe Relative Afferent Pupillary Defect
RAPD
No pupillary responses will be observed in either eye when the light is shown in the left eye.
Can be secondary to optic neuritis, optic nerve compression, central retinal artery occlusion, wide-spread retinal degeneration.
Pupillary Resonse for Partial Lesion CN 3
Right pupillary responses normal. Left pupil unresponsive to all stimuli. Eye position consistent with CN 3 involvement.
Secondary to partial lesion of CN 3 affecting parasympathetic fibers.
Differential for CN 3 Defect vs RAPD based on pupils
Ipsilateral defect in response for CN 3.
No response with either eye for RAPD.
Phototransduction Cascade
Draw
Leber congenital amaurosis
Inherited Retinal Disease @ Guanylate Cyclase
Cone/rod dystrophy
Cone dystrophy
Inherited Retinal Disease @ GCAP -> GTP -> impacting cGMP
Retinitis pigmentosa
Inherited Retinal disease @ R* .
Five classes of Rx for inherited photoreceptor degenerations:
Environmental modification
Nutritional supplementation
Toxin avoidance
Five classes of Rx for inherited photoreceptor degenerations:
Drugs
Small-molecule drugs (e.g., vitamins)
Large-molecule drugs (e.g., growth factors)
Five classes of Rx for inherited photoreceptor degenerations:
Gene therapy
Gene replacement
Mutant alllele suppression
Large-molecule drug delivery
Five classes of Rx for inherited photoreceptor degenerations:
Cell Therapy or Prosthesis
Cell therapy:
- Replacement of differentiated cell function
- Replacement of supportive cell function
- Large molecule drug delivery
Retinal prostheses
Visual pigments designed to absorb light
The amino acid sequence surrounding the retinal binding pocket determines the absorption characteristics of the pigment
11-cis-retinal
“Visual pigment protein”
Accomodation
I. The mechanism by which the eye changes focus from distant to near images.
Ii. This phenomenon is produced by a change in lens shape resulting from the action of the ciliary muscle on the zonular fibers. The lens substance is most malleable during childhood and the adult years, progressively losing its ability to change shape with age.
Iii. After ~40 years the rigidity of the lens nucleus reduces accommodation because the sclerotic nucleus cannot bulge anteriorly and change its anterior curvature as it could before.
Types of Accomodation
Types of Accomodation
Focus on near objects:
Contraction of the ciliary muscles, reduced diameter of muscular ring leading to relaxed zonular fibers, increased convexity and refractive power of lens
Focus on distant objects:
Relaxation of ciliary muscles, increased diameter of muscular ring leading to tautness of zonular fibers, flattening of central portion and decrease in refractive power of lens.
Pupillary reflex
I. Pupillary light reflex involves adjustments in pupil size with changes in light vessels.
Ii. The reflex is consensual: normally light that is directed in one eye produces pupil constriction in both eyes.
Ii. The direct response is the change in pupil size in the eye to which the light is directed (e.g., if the light is shone in the right eye, the right pupil constricts.
Iii. The consensual response is the chnage in pupil size in the eye opposite to the eye to which the light is directed (e.g., if the light is shone in the right eye, the left pupil also constricts consensually
Ii. The pupillary light reflex allows the eye to adjust the amount of light reaching the retina and protects the photoreceptors from bright lights. The iris contains two set of smooth muscles that control the size of the pupil.
Optic cupping
Optic cupping indicative of glaucoma; eye is putting pressure on the vascular supply that goes to the optic nerve
Image of vasculature going away from you.
Typically peripheral loss with glaucoma is common
Convergence
There are 5 million cones and 120 million rods and only 2 million ganglion cells.
Therefore, many receptors must send signals to each ganglion cell.
This is called convergences
The extent of convergence on different parts of retinal determines a trade off between sensitivity to low light levels and resolution of fine spatial detail.
Low Convergence Circuit
Driven by cones
1 cone: 1 bipolar cell: 1 ganglion
AKA one-to-one pairings
Found in fovea
Promotes spatial acuity
High convergence circuit
Driven by rods
Many rods: 1/2 rods bipolar cells: 1 ganglion
Ex: 8 rods: 4 bipolar cells: 1 retinal ganglia
AKA many-to-one convergence
Found in edges of macula but primarily in peripheral retina visual periphery
Promotes sensitivity in low light conditions and detect changes in position of stimuli in dim light.
M ganglion
8%
Important for detecting movement and changes in dim light or luminance.
P ganglion
80%
Importnat for processing info about shape/size/color of objects. Also, encode wavelengths of light via S + L + M cones.
Neurons Receptive Field
A ganglions receptive fied is based upon the SUM OF ITS INPUTS.
The area within the receptive field is divided into two regions, center and surround.
Two types of ganglion cell receptive fields
ON center/OFF surround Cell: Excitation from the small spot of light center and inhibition from the surround.
OFF center/ON surround cell: Inhibition from small spot of light center and excitation from the surround.
Describe how the visual field maps onto the retina
Light from LEFT visual field will hit NASAL side of left eye and TEMPORAL side of right eye.
Light from R visual field will hit TEMPORAL side of left eye and NASAL side of right eye.
Light from inferior visual field will be interpreted by DORSAL/superior retinal quadrants @ geniculocalcarine radiation and meyers loop
Light from superior visual field will be interpreted by VENTRAL/inferior retinal quadrants @ geniculocalcarine radiation and meyers loop
Describe how visual field information is organized as it travels through the optic chiasm to the LGN and then onto the primary visual cortices
Visual field ->
Retina ->
Optic Chiasm ->
LGN
Info on one side of visual field (R vs L) will stimulate the IPSILATERAL NASAL retina and the CONTRALATERAL temporal retina.
Info in R visual field stimulates R nasal retina and L temporal retina
Info in L visual field stimulates L nasal retina and R temporal retina
Info on one side of visual field (R vs L) will be processed by the CONTRALATERAL LGN and visual cortex.
Describe how visual fied information is organized as it travels through the optic chiasm to the LGN and then onto the primary visual cortices
Key to remember
Primary visual area (= striate cortex)
The cerebral cortex receives the encoded images of the contralateral visual FIELDS of both eyes.
Never forget that the image on the retina is INVERTED.
Describe how center-surround and simple receptive fields are related to each-other and what they encode.
Center-surround fields of the individual layer IV pyramidal neurons in the primary visual cortex (that are the same as ganglion neurons and LGN neurons) are summed together to produce the simple receptive fields of neurons on which the layer IV neurons synapse.
In terms of what they encode, CENTER-SURROUND is location of light. Simple fields add in ORIENTATION of light stimulus.
Explain how the complexity of receptive fields of neurons that process visual information increase as the information moves from layer IV in the primary visual cortex to the cortical areas below the primary cortex
The receptive field of a neuron represents the SUM OF THE FIELDS of the neuron that it synapses with.
As visual information processing moves into temporal and parietal lobes, there are several changes that occur in terms of receptive field:
1) Expansion of receptive fields
2) Loss of retinotopic organization
3) Increase in ability of stimulus to elicit a response regardless of location, distance, size or orientation
4. Increase in complexity of stimuli that elicit responses
5. Prior experience (recognition as well as importance) shape responses.
Overall, parietal and temporal vision areas contribute to interpretation of visual input.
DORSAL STREAM; motion and location tasks/”where”
VENTRAL STREAM: color and form/”what”
Visual Info Encoding by Neural Retina….
is highly organized as it moves through the visual system (particularly at LGN and striate cortex or cortical layer IV)
Information sent from the LGN to the primary visual cortex is segregated with regard to the eye of origination. This retinotopic aspect of the information is lost as the information is processed by higher other cortical areas.
Binocular vision
Vision using two eyes with overlapping fields of view allowing perception of depth.
Visual Inputs to LGN
Are from CONTRALATERAL VISUAL field but IPSILATERAL eye of origin
Inputs to the LGN are segregated by eye of origin
Macular representation of visual field…
..is largest in V1
Visual Field Lesions:
Optic Nerve Lesion
Monocular blindness or IPSILATERAL anopia
Visual Field Lesions:
Optic Chiasm Lesion
Heteronymous bitemporal hemianopsia
Visual Field Lesions:
Optic Tract Lesion
CONTRALATERAL homonymous hemianopsia
Visual Field Lesions:
Optic Radiation Lesion @ Temporal/Meyers loop
CONTRALATERAL superior homonymous quadrantanopsia
Visual Field Lesions:
Optic Radiation Lesion @ Parietal/Barums loop
CONTRALATERAL inferor homonymous quadrantanopsia
Visual Field Lesions:
Visual/Occipital cortex.
CONTRALATERAL homonymous hemianopsia with macular sparing.
Goldman Perimeter
Visual field exam device which uses computerized perimetry to MAP patients ability to see light and map their visual field.
Taste buds
Circumvalitae (posterior tongue, within sulcus are actual buds)
Foliate (lateral tongue, within sulcus are actual buds)
Fungiform (anterior tongue, top of gyrus is one superior bud)
All taste/buds receptors are MODIFIED EPITHELIAL CELLS at target organ of PNS. 1st synapse occurs here.
Modified Epithelial Cells:
Type 1
Detects salty
Glial-like
Ion channels
Modified Epithelial Cells:
Type 2
Detects sweet, umami and bitter
G-protein coupled receptors (GPCR)
Metabotropic channels
Modified Epithelial Cells:
Type 3
Detects acids Integrates with Type 2 (receives downstream affect of GPCR) Ion Channel (acid sensitive; e.g., citric acid)
Gustatory signal transduction
Salty/Sweet/Umami/Bitter Salty goes through ION channel Sweet Umami bitter goes through GPCR For both... Na+ K+ DEPOLARIZE CELL Ca2+ rushes in Triggers SERATONIN RELEASE into synaptic cleft Goes to seretonin receptors of afferent fibers from 7, 9, 10
THEORIES OF stimulus coding of taste (chemosensation) in the periphery
2 THEORIES
Across fiber: each class of receptors share affinity for MULTIPLE stimuli and contributes to perception (i.e., diffuse capacity) This is NOT what happens.
Labeled Line Principal: each receptor responds to LIMITED stimuli and sends DIRECT line to brain (i.e., topographic organization)
This IS what happens with taste; evidenced by ablation studies in rodents.
Stimulus coding of taste (chemosensation) in the periphery
Sensory afferent information from posterior 1/3 of tongue from CN IX, anterior 2/3 of tongue from CN VII and epiglottis from CN X travels to…
rostral NTS (gustatory NTS)/DSG within rNTS…
rNTS also receives bidirectinal input from hypothalamus for autnomic functions; amygdala for reward/emotional functions.
rNTS sends information to VSG (reticular formation, salivatory nucleus, dorsal motor nucleus of X)
rNTS also sends information to VPM of thalamus. VPM of thalamus communicates with somatosensory cotex (sensation), insula (disgust), frontal cortex (decisions/planning with PO)
Information from VSG + all cortical association areas go to NA for motor control of swallow.
Disorders of taste
hypoguesia, dysguesia, aguesia
secondary to many things but HEDGEHOG INHIBITOR
Rx for cancer treatment. Degrates taste buts BUT stem cells remain intact/taste can “regenerate”.
Characteristics of odorants
Small molecules (200 Da)
Volatile, readily vaporized
Lipid soluable
Includes acids, esters, alcohol, aldehydes, aromatics
Human olfaction able to discriminate ENANTIOMERS (i.e., mirror image compounds)
Smell Cells
Reside in psuedostratified epithelium
Can be neuronal or non neuronal
Non-neuronal smell cells
SuS (support cells 15%)
Bowman gland cells (excretion in nasal cavity)
Neuronal smell cells
Basal stem (5-10)%; give rise to new OSN’s consistently.
Globuse basal stem cells are ACTIVE
Horizontal basal stem cells are our RESERVE
OECs are glial cells that surround axon bundles
Olfactory Sensory Neurons (OSNs) make up 75%
They are signal transducing and have a limited lifespan
Olfactory signal transduction
Olfactory Sensory Neurons (OSN) or Olfactory Receptors (OR)s are at the cilia in the epithelium.
Note: 1 type of OR expressed in each cell but MANY ORs (ex: 1 gas receptor on every OSN)
Metabotropic channel activated with Gprotien (Golf)
Activates adenyl cylase
Activates cAMP (second messenger) to open cAMP gated channels
Na+ K+ DEPOLARIZATION
Ca2+ Influx
Neurontransmitter release @ synaptic cleft
To olfactory bulb
Stimulus coding of smell in the periphery
Olfactor receptors @ epithelium are stimulated; courses through the cribiform plate
Reaches OLFACTORY BULB where it goes to its deisgnated GLOMELURUS (detects the DOMINANT odor)
Synapses with MITRAL cells
Olfactory tract/CN1
Terminates @ multiple cortical olfactory regions: pyriform cortex, olfactory tubercle, amygdala and entorhinal cortex.
Pyriform cortex communicates with OFC (reward/pleasure/addiction/living with ID)
Olfactory tubercle AND Amygdala communicate with OFC/thalamus/hypothalamus (autonomic, salivating secondary to retronasal olfaction)
Entorhinal Cortex communicates with hippocampus (memories associated with smell/limbic-emotional system)
Olfactory disorders
Ciliopathies: cilia at olfactory receptors disordered
Channelopathies: dysfunction in ion channels (impt for transduction)
Kallman syndrome: developmental disorder (no olfactory bulb or OSN axon)
Anosmia: no smell (can be conductive or sensorineural)
Pharmacologica: ZINC destroys it (Zicam)
Degenerative-age: Sense of smell loss in PD secondary to reduction and distribution changes of glomeruli
Anosmia
Hyposmia
Parosmia
Phantosmia
Anosmia (loss of olfactory function)
Hyposmia (reduced ability to smell)
Parosmia (normal/pleasant odor smells foul)
Phantosmia (sensation of odors not present)
Loss of G-proteins or adenyl cyclase in mouse models has demonstrated ability to ablate all olfactory function.
Mutations in some of these genes Golf, cAMP has been found in people who are unable to smell.
Key Tenants of Stimulus Coding
Detection of all relevant chemicals in the environment (novel and old)
Encoding quality and quantity of individual chemicals in the context of complex chemical mixtures
Decode and interpret sensory information (i.e., cognitive appraisal to generate an appropriate behavioral response)
General Gustatory System
Nonvolatile, biologically relevant compounds Sweet Salty Sour Umami Bitter
General Olfactory Subsystems
General chemical odorants (volatiles) as well as peptides and pheromones
General Trigeminal Chemosensory System
Polymodal nociceptive neurons
Detect chemical irritants such as sulfur, ammonia, ethanol, capsaicin
Odors are detected by…
…specific G-Protein coupled receptors.
Only 1 type of OR is expressed in each cell.
Receptors localize to the cilia
Distinct odor receptor expression…
…gives every neuron a specific response profile.
Different levels of responses to odor A , B, C, but will have a DOMINANT response.
Smell across mammals…
across species neuronal numbers in olfactory bulb is relatively consistent.
Summary of Qualities of Chemosensory Systems:
Detection of millions of distinct chemical stimuli
Coding allows individual odor molecules to be discriminated
Overlap in receptor expression provides a single taste perception to chemicals
Summary of Qualities of Chemosensory Systems:
OSNs and taste cells directly contact external environment
OSNs only cell type to directly innervate the CNS (CN 1 is OSN axons)
Taste cells synapse with CN fibers in the taste bud
Summary of Qualities of Chemosensory Systems:
Sensory cells undergo constitutive neurogenesis
Entire OE can be regenerated following injury
Taste buds/taste cells replaced throughout life
