Limbic System Part 1: Emotions/Memory

Limbic system

participates in complex behaviors such as, memory and learning, and it is thought to be the neuro-anatomical substrate for emotional, drive-related, and motivated aspects of behavior

• includes both cortical and subcortical structures

first level of the limbic system

first level: limbic lobe (structures are interconnected)

• subcallosal area

• cingulate gyrus

• parahippocampal gyrus (entorhinal cortex)

• uncus

• hippocampal formation

Second level of limbic system

these structures are interconnected with each other and structures of the limbic lobe

• prefrontal and orbitofrontal cortex: conscious perception of emotions and emotional regulation

• amygdala: formation of emotional memories; basic drives

• septal nuclei: involved in reward circuitry

• nucleus accumbent (ventral striatum) and ventral pallidum - part of limbic loop (reward circuitry)

• hypothalamic nuclei (esp. maxillary bodies): important role in producing the visceral responses to emotions

• midbrain (ventral tegmental area): important source of dopamine for reward circuit

• thalamic nuclei: integrate and gate information flow to cortex

• habenular nuclei: role in control of emotional and social behaviors related to pain, stress and anxiety, role in sleep

Limbic system functional link

connects the neocortex and hypothalamus: forming functional link between endocrine, visceral, emotional, and voluntary responses to the environment

prefrontal and orbitofrontal cortex

• prefrontal and orbitofrontal cortex: conscious perception of emotions and emotional regulation

amygdala

• amygdala: formation of emotional memories; basic drives

septal nuclei

• septal nuclei: involved in reward circuitry

nucleus accumbens and ventral pallidum

• nucleus accumbens (ventral striatum) and ventral pallidum - part of limbic loop (reward circuitry)

hypothalamic nuclei

• hypothalamic nuclei (esp. maxillary bodies): important role in producing the visceral responses to emotions

midbrain

• midbrain (ventral tegmental area): important source of dopamine for reward circuit

thalamic nuclei

• thalamic nuclei: integrate and gate information flow to cortex

habenular nuclei

habenular nuclei: role in control of emotional and social behaviors related to pain, stress and anxiety, role in sleep

Select the structures that are in the first level of the limbic system.

Subcallosal area

Amygdala

Nucleus accumbens

Parahippocampal gyrus

Hippocampus

Orbitofrontal cortex

subcallosal area

parahippocampal gyrus

hippocampus

cingulate cortex

Select the structures that are in the second level of the limbic system.

Amygdala

Hippocampal formation

Hypothalamus

Prefrontal cortex

Uncus

Thalamic nuclei

amygdala

hypothalamus

prefrontal cortex

thalamic nuclei

memory and learning

normal ability to learn, store, and retrieve information is critical to everyday life and disruption of this normal ability can have profound effects on engagement in occupation

learning

acquisition of knowledge

memory

retention of learned information; ability to retain information over time

• encoding: sensory input changed into a form that the brain can process

• consolidation/storage: how long the memory lasts, how much info can be stored/capacity, what type of info is held

• retrieval: getting info out of storage

immediate memory

memory that spans seconds; sensory perception sh

short term memory

working memory

involves the short-term maintenance of information in memory and the manipulation of information to achieve an immediate goal (e.g. retaining the phone number you just looked up to order pizza) - prefrontal cortexl

long-term memory

memory that spans days, months, and years

2 types: declarative and non-declaratived

declarative memory

explicit memory

memories of facts and events that can be consciously recalled (who, what, when, where)

• hippocampus

• semantic memory: involves the knowledge of facts

• episodic memory: memory for events and includes that slitty to learn, store, and retrieve information about personal experiences attached to a specific event, including the time, place and details of the event

non-declarative memory

implicit or procedural memory

memories that cannot be consciously recalled - subconscious behavioral or physiological response to events or stimuli

• memories for skills and habits (procedural memory): knowing how to do it or motor memory

  • basal nuclei and cerebellum

  • examples: riding a bike, swimming, driving

• associative learning: stimulus-response learning in which a new response becomes associated with a particular stimulus (e.g. classical conditioning)

  • includes emotional associations (aka emotional memories): changes in behavior toward a previously neutral stimulus secondary to experience - amygdala

    • examples: fear and reward

Hippocampal formation

aka hippocampus

plays major role in mediation of learning and declarative memory formation

3 zones

• subiculum

• hippocampus proper

• dentate gyrus

subiculum (hippocampus zone)

transition zone of cortex that is continuous with the hippocampus on one side and the para-hippocampal gyrus on the other side

hippocampus proper (hippocampus zone)

consists of gray matter and a thin sheet of white matter (laves) which are the axons of the cell bodies located in the subiculum and the hippocampus proper

dentate gyrus (hippocampus zone)

area of gray matter that lies between the fimbria and the parahippocampal gyrus

coronal section of brain/hippocampal formation

hi

hippocampal formation: neural circuitry

afferent pathways

• perforant pathway: hippocampus receives the majority of its input from the parahippocampal grays (entorhinal cortex) - most fibers terminate not he granule cells of the dentate gyrus

• granule cells of the dentate gyrus project to the hippocampus which will then provide input into the subiculum

• subiculum also receives input from the amygdala

efferent pathways

• output from the hippocampus originates predominately from the subiculum and some of the pyramidal cells of the hippocampus proper

• fornix: major efferent pathway of the hippocampus

  • fibers from the subiculum project via fornix to the medial mammillary nucleus (mammillary bodies of the hypothalamus)

  • fibers from the hippocampus proper project via the fornix to the septal nuclei, the medial frontal cortex, hypothalamic nuclei, and the nucleus accumbens

long-term potentiation (see extra video)

short term memories are consolidated into long-term memories through a process called long-term potentiation (LTP)

LTP causes long-term strengthening of the synapse between two neurons that were activated at the same time “cells that fire together - wire together”

• low frequency stimulus: glutamate released from presynaptic cell binds both NMDA and AMPA receptor types; activates AMPA receptor but insufficient to activate NMDA

  • high-frequency stimulus: synaptic inputs (excitatory post-synaptic potentials - EPSPs) are spatially and temporally summed causing significant depolarization of the post-synaptic cell membrane resulting gin (removal of Mg++) activating NMDA receptor on the post-synaptic neuron

Long-term potentiation

glutamate released at the performant pathway activates NMDA receptors in hippocampal cells that allow an increased number of Ca2+ (calcium) ions to enter the cell

• Ca2+ influx causes biochemical changes that trigger long-term changes (e.g. the insertion of more glutamate receptors into the post-synaptic membrane, greater neurotransmitter release, dendritic spine growth, etc.)

synaptic plasticity occurs: the more the circuit is activated, the easier it is to activate it - resulting in learning and memory

long term memories are then ultimately stored in the cortex

Clinical: alzheimer disease

early disease process: characterized by the progressive loss of declarative memory with poor recall of recent events and difficulty with new learning

late disease process: loss of long-term memory and behavioral changes later in the disease process; non-declarative memory is relatively spared

neuronal loss in the hippocampus and parahippocampal gyrus

Korsakoff’s syndrome

results from thiamine deficiency; caused by alcohol abuse, dietary deficiencies, or the effects of chemotherapy

characterized by loss of short-term memory, an inability to establish long-term memory for new events and confabulation

neuronal loss in the mammillary region of the hypothalamus and the hippocampuste

temporal lobe epilepsy

hippocampus is a frequent side of recurrent seizure activity which may result in progressive memory impairment and changes in emotional behavior

True or false? Long-term potentiation involves activation of NMDA receptors, which allow Ca2+ (calcium) ions to enter cells of the hippocampus.

This is true. In the LTP process, glutamate that is released by the perforant pathway ultimately ends up activating NMDA receptors in hippocampal cells. This allows calcium to enter the cell. This calcium influx induces biochemical changes in the cell, such as the insertion of more glutamate receptors in the post-synaptic membrane, greater release of neurotransmitters, and dendritic spine growth. This results in synaptic plasticity – the more a circuit is activated, the easier it becomes to activate it, which results in learning and memory.

Jon rode his bike to the park. This activity involves…

procedural memory

Riding a bike involves procedural memory, or knowing how to do something.

true or false? Korsakoff's syndrome may result in memory loss due to recurrent seizures in the temporal lobe.

This is false. Memory impairment can occur in temporal lobe epilepsy due to recurrent seizures in the hippocampus. Korsakoff's syndrome results from thiamine deficiency and is caused by alcohol abuse, dietary deficiencies, or the effects of chemotherapy.

true or false? Janet is listening to a neuroscience lecture and taking notes. This involves her short term working memory.

This is true. This activity involves short-term maintenance and manipulation of information.

emotions: historical perspective

James-lange 1800s: William james and carl lange

• suggested emotions occur as the direct result of a physiological reaction to an external stimulus or event

• example: we see a bear in the woods (external stimulus), and we have a physiological response to that stimulus (fight or flight), the interpretation of that response results in the emotional experience (e.g. fear)

cannon-bard (1920-1930s): Walter cannon and Philip bard

• challenged James-lange

• we can have physiological reactions without emotions (increase heart rate with exercise, but no emotional experience)

• the same physiological reaction may occur with different emotional experiences (e.g. heart racing with fear; heart racing with excitement; cry with joy; cry with sadness)

• emotional experience happens too quickly for it to be purely a byproduct of the physiological reactions

• proposed the two occur together: links between brain regions that cause both the emotional experience and physiological reactions

Emotions: historical perspective; schachter-singer

schachter-singer (1960s)

• stanley schachter and Jerome singer - two factor theory

• combined elements of James-lange and cannon-bard

• highlighted the importance of reasoning in emotions

• proposed that emotions results from both physiological and cognitive processes

• when an event causes physiological arousal, we try to find a reason for this arousal, this process results in the experience of emotion and the labeling of the emotion

emotions: current views

high-order theory of emotional consciousness

• recognizes the importance of both physiological and cognitive processes in emotions

• parallel-distributed processing in subcortical and cortical circuits give rise to emotions and bodily responses to emotions

  • sub-cortical circuits (aka survival circuits) allow for the implicit evaluation of a stimulus as potentially harmful or beneficial and mobilize adaptive responses that allow us to suervice

  • cortical areas are engaged in the higher-level processing that allows us to ultimately understand and experience the stimulus leading to the experience of emotions

• general networks of cognition (GNCs) allow us to have thoughts and reflex on our own mental states and the states of others

  • GNCs create “higher order representations” of external stimuli

  • related to our working memory

• requires an extended network of interconnected brain structures

emotions: current views

neuroanatomical substrate of emotions: expanded paper circuit - consists of multiple networks that are interconnected

• amygdala: key structure in emotional expression, formation of emotional memories, basic drives (fear/reward), associative learning

• hippocampus: plays a key role in the formation of declarative memories and is involved in emotional processing and regulation (coupled with the amygdala)

• hypothalamus: involved with generating the bodily expressions of emotions, physiological responses

• association areas of the cortex and the prefrontal cortex: play a key role in the conscious experience of emotions and modulating behavior in response to emotions

amygdala

functions as an integrative center for emotional behavior

• critical for the ability to feel strong emotions such as fear and pleasure

• important for recognizing and interpreting the emotions of others

• appears to play a major role in linking perception/memories with visceral and behavioral responses (associative learning)

• assesses emotional significance

efferents of the amygdala are sent to

hypothalamus - regulation of bodily responses to the emotion

dorsomedial nucleus of thalamus and orbitofrontal cortex - conscious perception of emotion

hippocampus and associated cortical areas (medial temporal lobe memory system) - consolidation of emotional memories

kluver-bucy syndrome

bilateral temporal lobe lesions that abolish he amygdala and adjacent structures (e.g. hippocampus can be involved to varying degrees)

• visual agnosia: inability to recognize objects by sight

• hyperorality: tendency to examine objects excessively by mouth

• placidity: no longe rhos fear or anger when appropriate to situation

• hyrerphagia: excessive eating

• hyper sexuality: suggestive behaviors and suggestive talk

diffuse modulatory systems

collections of neurons that make widely dispersed and diffuse connections throughout the brain; they perform regulatory functions, modulating activity in vast populations of postsynaptic neurons

the core of each system has a small set of neurons (several thousand) that release the same neurotransmitter; they arise predominantly from the brainstem

each neuron of the system can influence many others through divergence (one presynaptic axon can contact about 100,000 post-synaptic neurons throughout the brain)

these systems are important to overall brain function impacting motor control, memory, mood, motivation, and metabolic state

many psychoactive drugs impact these systems and imbalances in these systems factor into proposed theories of the biological basis of mental illness

diffuse modulatory systems

• ventral tegmental area (VTA)/substantia nigra (SN) - dopamine

  • reward system (VTA); learning motor skills/habits that produce rewards (SN)

• raphe nuclei - serotonin

  • involve din control of pain modulation, sleep-wake cycles, mood and emotional behaviors

• locus coeruleus - norepinephrine

  • involved in the regulation of attention, arousal, sleep-wake cycles, learning, memory, anxiety, pain, mood, and brain metabolism

• basal forebrain - acetylcholine

  • regulate brain excitability during arousal and sleep-wake cycles and playing a role in learning and memory formation

reward circuitry

reward is a key factor for driving incentive-based learning and the development of goal-direct behaviors

structural components of the reward circuit

• ventral tegmental area (VTA) of the midbrain: releases dopamine in response to pleasurable stimuli

• nucleus accumbens (ventral striatum): major target of dopamine (thought to be the brain’s pleasure center)

• amygdala: associative learning (pairing of the stimuli and the feeling of pleasure)

• prefrontal cortex: regulates executive functions

• hippocampus: explicit memory formation (episodi)

mesocorticolimbic pathway

the ventral tegmental area (VTA) in the midbrain sends dopaminergic projections to the limbic system and cortex

mesocortical projections: VTA to PFC

mesolimbic projections: VTA to nucleus accumbens, amygdala, hippocampusre

reward circuitry

hijacking the reward circuitry

addiction: brain disorder; risk is influenced by genes, environment, neurochemical

neurobiology of addiction: drug-induced euphoria occurs as a result of drug effects on the mesocorticolimbic system (mediated by increased levels of dopamine in the system)

• chronic substance use can change the structure and function of the reward system and these changes can last years after a person ceases to use the substance

  • tolerance and dependence; cravings; sensations

• alterations in frontal lobe result in distorted learning and memory: overvaluing of the reward associated with the substance use; undervaluing the risks associated with obtaining the reward, and inability to connect the drug use with negative consequences

  • sustained activation of glutamate - impacting memory and learning

• evidence suggests that people with low levels of D2 receptors are at risk for addictions (e.g. drugs, food, and other compulsive behaviors)

drugs and diffuse modulatory systems: hallucinogens

LSD (lysergic acid diethylamide) - chemical structure similar to serotonin and appears to act on the serotonergic system

• causes dreamlike state with heightened awareness of sensory stimuli and mixing of perceptions

• current research suggests LSD causes hallucinations by overriding the naturally modulated release of serotonin in cortical areas involved in perception formation and interpretation

drugs and diffuse modulatory systems: stimulants

stimulants: cocaine and amphetamines - interact with the catecholamine systems (dopamine and norepinephrine)

• both give users a feeling of increased alertness and self-confidence, sense of exhilaration and euphoria, and decreased appetite; mimic activation of the sympathetic division of the ANS

• cocaine block reuptake of dopamine; amphetamines block reuptake of both dopamine and NE and stimulates release of dopamine

• hijacks the mesocorticolimic dopamine system - reinforcing drug seeking behaviors and compulsive use

True or false? The Papez circuit includes the amygdala.

The Papez circuit is an early view of the neuroanatomy of emotions and did not include the amygdala. The structures included in the circuit of Papez are the cingulate cortex, the hippocampus, the hypothalamus (mammillary bodies), and the anterior nuclei of the thalamus.

The mesocorticolimbic pathway (rewards system) involves dopaminergic projections from…

the ventral tegmental area to the ventral striatum, amygdala, hippocampus, and prefrontal cortex.

The mesocorticolimbic pathway (rewards system) involves dopaminergic projections from the ventral tegmental area to the ventral striatum, amygdala, hippocampus, and prefrontal cortex.

In the higher order theory of emotional consciousness, subcortical survival circuits primarily generate emotions.

This is false. In the higher order theory of emotional consciousness, both subcortical and cortical circuits contribute to the perception of emotions, through parallel-distributed processing.

extra video: LTP in the hippocampus