article 1 : Nueral systems and the emotion-memory link Flashcards
Nueral systems and the emotion-memory link
Mark G. Packard, Ty Gadberry, Jarid Goodman
abstract
context and scope:
- This is a brief review article prepared for a Special Issue
- The focus is on summarizing original research about how emotions modulate memory
Historical background:
- Highlights the pioneering work of James L. McGaugh and colleagues
- This work laid the foundation for understanding the emotion-memory link
Post-training drug administration studies:
- Describes early research demonstrating that drugs administered after training can affect memory consolidation
- Specifically emphasizes the role of epinephrine, a stress hormone
- These studies were crucial in establishing the concept of memory modulation
Basolateral amygdala’s role:
- Discusses the discovery that the basolateral amygdala plays a critical role in how emotions modulate memory
- This finding was a significant advancement in understanding the neural basis of emotional influences on memory
Multiple memory systems approach:
- Introduces the concept of multiple memory systems in the brain
- Focuses on two key systems:
a. Hippocampus: associated with cognitive memory, including spatial, explicit, and declarative memory processes
b. Dorsolateral striatum: linked to habit memory, particularly stimulus-response (S-R) associations
- This approach provides a framework for understanding how different types of memory might be affected by emotions
Emotional arousal effects on memory systems:
- Presents findings that strong emotional arousal can influence which memory system is predominantly used
- Specifically, emotional arousal tends to bias both animals and humans towards using habit memory (associated with the dorsolateral striatum)
- This suggests that emotions don’t just strengthen memories, but can change the type of memory formed
Modulatory role of the basolateral amygdala:
- Explains that the shift towards habit memory under emotional arousal depends on the basolateral amygdala’s modulatory function
- This highlights the amygdala’s role not just in emotional processing, but in regulating how other brain regions process information during emotional states
Implications for psychopathology:
- Briefly touches on the potential relevance of these findings to human mental health
- Suggests that the enhancement of dorsolateral striatal-dependent (habit) memory by emotions might help explain some maladaptive habitual behaviors seen in certain psychological disorders
- This points to the clinical relevance of understanding the emotion-memory link
Methodology and evidence base:
- While not explicitly stated, the abstract implies that the review covers both animal and human studies
- This suggests a translational approach, bridging findings from animal models to human behavior and cognition
Theoretical significance:
- The abstract outlines a coherent theory linking emotional arousal, specific brain regions (amygdala, hippocampus, dorsolateral striatum), and shifts in the type of memory formed
- This integrative approach demonstrates how research in this field has moved from isolated findings to a more comprehensive understanding of emotion-memory interactions
AI notes
Introduction and Historical Context
1. Ancient recognition of emotion’s effect on memory
- Recognized in ancient medical and philosophical texts
- Hippocrates (460 BCE): Noted emotions’ capacity to enhance and impair memory
- Rhetorica ad Herrenium (1511): Drew from contemporary philosophical theories to explain emotion-memory phenomena
Modern approaches to understanding emotion
- Multiple theoretical and methodological approaches exist
- Damasio (1994, 1999): Emphasized role of bodily states in emotion and cognition
- Ekman & Davidson (1994): Focused on facial expressions and discrete emotion categories
- Lane & Nadel (2000): Explored cognitive neuroscience of emotion
James L. McGaugh’s pioneering work
- Pivotal in understanding emotional modulation of memory
- Elucidated underlying neural mechanisms
- His work served as a catalyst for decades of neurobehavioral research worldwide
Early Research on Memory Consolidation
1. Clinical and experimental findings on post-training memory state
- Burnham (1903): Early observations on retrograde amnesia
- Duncan (1949): Studied effects of electroconvulsive shock on memory
- Zubin & Barrera (1941): Investigated amnesia in relation to emotional states
- Müller & Pilzecker (1900): Introduced concept of memory consolidation
- Hebb (1949): Proposed neurophysiological basis for memory formation
McGaugh’s discovery of post-training drug effects
- Breen & McGaugh (1961): First demonstration that post-training drug treatments can facilitate memory consolidation
- Initially focused on stimulant drugs
Characteristics of post-training treatments
- Time-dependent effects: Most effective when administered shortly after training
- Effectiveness decreases as training-treatment interval increases
- Time-dependency consistent with consolidation theory
Importance of post-training paradigm
- Allowed study of drug effects on memory without confounding performance factors
- Avoided potential issues with sensory, motoric, or motivational processes
- Critical for isolating effects on memory consolidation
Epinephrine and Hormonal Modulation of Memory
- Gold’s (1975) demonstration of epinephrine’s effects
- Conducted in McGaugh’s laboratory
- Used one-trial inhibitory avoidance task with rats and mice
- Post-training epinephrine injections facilitated memory in 24-hour retention test
- Time-dependent effects: injections delayed 30 minutes or 2 hours ineffective
Bi-directional effects of epinephrine
- Gold & McGaugh (1975): Showed epinephrine could enhance or impair memory
- Effects depended on dose and magnitude of aversive stimulus used in training
- Doses enhancing memory with lower foot-shock impaired memory with higher foot-shock levels
- Term “memory modulation” adopted to reflect this bi-directional effect
Early amygdala studies
- Ilyutchenok & Vinnitsky (1971), Gold et al. (1973), Kesner & Wilburn (1974): Found post-training electrical stimulation of amygdala impairs memory consolidation
- Gold et al. (1975): Showed memory modulatory influence of amygdala stimulation dependent on footshock levels and endogenous epinephrine levels
Amygdala’s role in epinephrine effects
- L Cahill & McGaugh (1991): Demonstrated excitotoxic lesions of amygdala block memory modulatory effects of peripheral epinephrine
- Indicated functional integrity of amygdala necessary for epinephrine-induced memory modulation
Peripheral action of epinephrine
- Epinephrine doesn’t cross blood-brain barrier
- C L Williams & McGaugh (1993): Showed initial peripheral site of action for epinephrine
- Process initiated via vagus nerve
- Uses nucleus of solitary tract in brain stem as relay for signaling the amygdala
Amygdala Model of Memory Modulation
McGaugh’s model of basolateral amygdala (BLA) in memory modulation
- McGaugh et al. (1996): Proposed comprehensive model
- Considered multiple neurotransmitter systems:
a. GABAergic
b. Noradrenergic
c. Opioid
d. Cholinergic
- Included peripheral influences of adrenergic and glucocorticoid systems on amygdala activity
Key features of the model
- BLA not considered a memory storage site
- Emotional arousal activates efferent amygdala pathways
- These pathways modulate memory consolidation processes in other brain structures
Role of stria terminalis
- Identified as critical output pathway for amygdala’s modulatory role
- Liang & McGaugh (1983): Showed stria terminalis lesions block effects of post-training epinephrine on memory
- McGaugh (2004): Demonstrated stria terminalis lesions attenuate memory modulatory effects of various neurotransmitter systems (noradrenergic, opioid, cholinergic, glucocorticoid)
- Stria terminalis lesions themselves do not impair memory, supporting modulatory hypothesis
Multiple Memory Systems and Amygdala Modulation
- Differential roles of hippocampus and dorsal striatum
- Packard et al. (1989), Packard & White (1991), Packard & McGaugh (1992), McDonald & White (1993): Established distinct roles in memory
- Hippocampus: cognitive memory
- Dorsal striatum: habit memory
Water maze experiments (Packard et al., 1994)
- Used hippocampus-dependent spatial task and dorsal striatum-dependent S-R task
- Post-training amphetamine infusions into different brain regions
- Results:
a. Dorsal striatal infusions selectively enhanced S-R task memory
b. Hippocampal infusions selectively enhanced cognitive task memory
c. BLA infusions enhanced memory in both tasks
Key finding: Amygdala’s promiscuous modulatory role
- BLA can influence multiple types of memory
- Demonstrates versatility of amygdala’s memory modulatory function
Emotional Modulation of Multiple Memory Systems (Animal Studies)
- Stress effects on memory systems (Kim et al., 2001)
- Used stressful experience (intermittent tail-shock and one-hour bodily restraint)
- Pre-training stress impaired spatial memory retention in water maze task
- Amygdala lesions blocked stress effects on spatial memory
- B Roozendaal & McGaugh (1997): Showed amygdala lesions block memory impairing effects of hippocampal glucocorticoid infusions
Dual-solution water maze task (Kim et al., 2001)
- Task allowed for both cognitive and S-R habit memory solutions
- Results:
- Stressed rats biased towards striatum-dependent S-R learning
- Non-stressed rats favored hippocampus-dependent spatial learning
- First evidence of stress “shifting” balance between memory systems
Pharmacological induction of anxiety (Packard & Wingard, 2004)
- Used α-2 adrenoreceptor antagonists (yohimbine, RS 79948-197)
- Anxiogenic drugs biased towards response learning in plus-maze task
- Effects seen with both systemic and intra-BLA drug administration
- Additional studies: Elliot & Packard (2008), Wingard & Packard (2008), Packard & Gabriele (2009), Leong et al. (2012)
Competitive interaction between memory systems
- Evidence of competition: hippocampal lesions enhance DLS-dependent learning
- References: McDonald & White (1993), Packard et al. (1989), Matthews and Best (1995), Schroeder et al. (2002)
- Emotional arousal may enhance DLS habit memory by impairing hippocampal function
Role of stress hormones
- Both noradrenergic and glucocorticoid systems implicated in biasing towards habit memory
- References: Medina et al. (2007), Schwabe et al. (2010), Guenzel et al. (2014), Goodman et al. (2015), Siller-Pérez et al. (2017)
Emotional Modulation of Multiple Memory Systems (Human Studies)
Translation to human studies
- Packard (2010): Reviewed evidence that differential roles of hippocampus and DLS in memory generalize across species
Schwabe et al. (2007) study
- Used Trier Social Stress Test (TSST) before a dual-solution learning task
- Task design based on animal studies (McDonald & White, 1994; Kim et al., 2001)
- Results:
- Stressed participants more likely to use stimulus-response strategy
- Non-stressed participants more likely to use spatial strategy
- Higher salivary cortisol levels associated with stimulus-response strategy use
Neuroimaging study (Schwabe & Wolf, 2012)
- Used probabilistic classification learning (PCL) task
- PCL task characteristics:
- Involves acquisition of probabilistic predictions
- Can be acquired through trial-and-error learning
- Knowlton et al. (1994): Proposed as exemplar of habit learning in humans
- Knowlton et al. (1996): Showed acquisition impaired in Parkinson’s disease
- Results:
- Stress associated with reduced explicit task knowledge
- Increased use of procedural strategies in stressed participants
- Correlation between striatal activation and task performance in stressed participants
- Salivary cortisol levels correlated with striatal activation during PCL task
Role of glucocorticoids and amygdala (Schwabe et al., 2013)
- Used mineralocorticoid receptor antagonist spironolactone
- Results:
- Spironolactone blocked stress-induced shift to procedural strategies
- Altered connectivity between amygdala, hippocampus, and striatum
- Indicates role for amygdala in orchestrating stress-induced shift in learning strategies
- Suggests mineralocorticoid receptor activity plays critical facilitatory role
Conclusions and Future Directions
-
Summary of findings
- Emotional arousal can impair hippocampal cognitive memory and enhance DLS habit memory
- Effects mediated by BLA
- Consistent across animal and human studies -
Broader neural systems involved
- Arnsten (1998, 2009): Showed stress may impair prefrontal cortex cognitive functioning
- This impairment may contribute to reliance on habitual behavior -
Complexities of emotional effects on memory
- Emotional arousal can enhance hippocampal memory under some conditions
- Baldi & Bucherelli (2005), Salehi et al. (2010): Described inverted U-shaped relationship between arousal and hippocampal memory -
Limitations of existing research
- Majority of studies used male rats
- Need for more research on female subjects and hormonal influences
- References: Korol et al. (2004), Quinlan, Hussain, & Brake (2008), Hussain, Cosset, & Brake (2015) -
Relevance to psychopathology
- Potential link between stress-induced habit memory bias and maladaptive behaviors in psychiatric disorders
- Relevant to understanding disorders like drug addiction, PTSD, OCD
- References: White (1996), Graybiel & Rauch (2000), Everitt & Robbins (2005, 2013), Schwabe et al. (2011)
6.** Future directions**
- Need for more research on early life stress and its long-term effects on memory systems
- Schwabe, Bohbot and Wolf (2021), Patterson, Craske and Knowlton (2013): Initial studies on early life stress and adult memory system use
What was James L. McGaugh’s key discovery regarding post-training drug treatments?
McGaugh discovered that post-training drug treatments can facilitate memory consolidation, demonstrating a way to study drug effects on memory without confounding performance factors.
How does epinephrine affect memory consolidation?
Post-training injections of epinephrine can facilitate memory in a time-dependent manner. Its effects are bi-directional, enhancing or impairing memory depending on dose and the magnitude of the aversive stimulus used in training.
What is the role of the amygdala in epinephrine-induced memory modulation?
The functional integrity of the amygdala is necessary for epinephrine-induced memory modulation. Excitotoxic lesions of the amygdala block the memory modulatory effects of peripherally injected epinephrine.
Describe the key features of McGaugh’s model of basolateral amygdala in memory modulation
The model proposes that the basolateral amygdala is not a memory storage site, but rather that emotional arousal activates efferent amygdala pathways to modulate memory consolidation processes in other brain structures.
What are the two main memory systems discussed in the context of emotional modulation?
The hippocampus-dependent cognitive/spatial memory system and the dorsal striatum-dependent stimulus-response (S-R)/habit memory system.
How does stress affect the relative use of hippocampal and dorsal striatal memory systems?
Stress tends to bias animals towards the use of striatum-dependent S-R learning and away from hippocampus-dependent spatial learning.
What effect do anxiogenic drugs have on the use of memory systems?
Anxiogenic drugs bias animals toward the use of striatum-dependent habit memory in tasks that can be solved by either cognitive or habit strategies.
How has the effect of stress on memory systems been demonstrated in humans?
Studies show that stressed participants are more likely to use stimulus-response strategies in learning tasks, similar to the habit memory bias seen in animal studies.Studies show that stressed participants are more likely to use stimulus-response strategies in learning tasks, similar to the habit memory bias seen in animal studies.
How do glucocorticoids affect memory systems?
Glucocorticoids can enhance dorsal striatal-dependent habit memory and impair hippocampal cognitive memory, similar to the effects of stress and anxiety.
What are the potential clinical implications of stress-induced habit memory bias?
The stress-induced habit memory bias may be relevant to understanding maladaptive habitual behaviors in certain psychiatric disorders, such as drug addiction, PTSD, and OCD.
What is the role of the stria terminalis in memory modulation?
The stria terminalis provides a critical output pathway for the memory modulatory role of the amygdala. Lesions of the stria terminalis block the effects of post-training epinephrine on memory and attenuate the memory modulatory effects of various neurotransmitter systems.
What is meant by the “promiscuous” role of the basolateral amygdala in memory modulation?
The basolateral amygdala can influence multiple types of memory, including both hippocampus-dependent cognitive memory and striatum-dependent habit memory.
What does the dual-solution water maze task reveal about stress effects on memory systems?
In this task, stressed rats tend to use striatum-dependent S-R learning strategies, while non-stressed rats favor hippocampus-dependent spatial learning strategies.
How have researchers used pharmacological methods to study anxiety effects on memory systems?
Researchers have used anxiogenic drugs like α-2 adrenoreceptor antagonists (e.g., yohimbine, RS 79948-197) to induce anxiety and study its effects on the use of different memory strategies.
What evidence suggests competition between hippocampal and striatal memory systems?
Studies show that hippocampal lesions can lead to enhanced dorsolateral striatum-dependent learning, suggesting these systems may compete for control over behavior.
How has the Trier Social Stress Test been used in human studies of stress and memory?
The TSST has been used to induce stress in human participants before they complete learning tasks. Stressed participants show a bias towards stimulus-response strategies, similar to the habit memory bias seen in animal studies.
What has neuroimaging revealed about stress effects on memory systems in humans?
fMRI studies show that stress is associated with increased striatal activation and decreased hippocampal activation during learning tasks, correlating with a shift towards procedural learning strategies.
How do mineralocorticoid receptors influence stress effects on memory systems?
Studies using the mineralocorticoid receptor antagonist spironolactone suggest that mineralocorticoid receptor activity plays a critical facilitatory role in the stress-induced shift towards habit memory.
What is the inverted U-shaped relationship between arousal and hippocampal memory?
This relationship suggests that moderate levels of arousal enhance hippocampal memory, while very low or very high levels of arousal impair hippocampal memory.
How might early life stress affect memory systems in adulthood?
Some evidence suggests that early life stress is associated with a predominant use of striatal-dependent habit memory in adulthood, but more research is needed in this area.
What is known about sex differences in stress effects on memory systems?
Most studies have used male subjects. In female rats, performance in place and response learning is influenced by ovarian hormone function and phase of the estrous cycle. More research is needed on stress effects in females.
