Brain and Behavior Exam 3

Engram

physical trace of memory that requires the activation of interconnected neurons across the brain

Richard Semon, 1904

a stimulus created a permanent record or enduring modification in the brain that can later be reactivated

karl Lashley

"Where is the engram stored?" - mass action principle and equipotentiality principle

Mass action principle

Extent of memory impairment in rats was proportional to the amount of brain tissue removed, rather than the specific location of the lesion

equipotentiality principle

When one part of the brain is damaged, other parts can sometimes take over the functions of the damaged area

Patient H.M

Bilateral temporal lobectomy to treat his severe epilepsy -- anterior 2/3 of hippocampus, some of entorhinal cortex, piriform cortex, and amygdala removed. Unable to form new memories

Hippocampal place cells

Fire when an animal is in a specific location, forming a place field. Work with other neurons in the hippocampus and surrounding regions to perform spatial processing

How memories are encoded into engrams

Neurons appear to be selected in part by their excitability and molecular state at the time of the experience. During encoding, synapses within these neurons undergo changes that strengthen the memory representation

Larger postsynaptic potential due to:

more neurotransmitter released, more receptors, more neurotransmitter released and more receptors

Long-Term Potentiation (LTP)

Strengthens the baseline activity at a synapse

Mechanisms of LTP

Stimulate with a burst of electrical activity --> many AMPA receptors activated; depolarization removes Mg2+ block; NMDA receptors activated; new AMPA receptors inserted into postsynaptic membrane; enhancement of subsequent transmitter release through retrograde signals

Long Term Depression (LTD)

Gill and Siphon withdrawal reflex in the Aplysia californica: disturb siphon and animal retracts gill to protect it

Short-term habituation

Repeatedly disturb siphon, the animal stops retracting gill. Sensory neurons release less neurotransmitter

Long-term habituation

If you disturb the siphon the next day, the animal retracts gill. But if you disturb repeatedly, animal stops retracting gill faster due to loss of some synapses (animal knows it isn't in danger)

Hormones

Chemical signals. Travel throughout the body via bloodstream and act on specific receptors. Secreted by specialized cells (glands)

Endocrine communication

a hormone is released into the bloodstream to act on target cells/organs

Hormone release

Endocrine glands release hormones within the body. Exocrine glands release hormones and other fluids outside the body

Neurotransmitters

synaptic communication involves chemical release and diffusion across a synapse

Paracrine communication

a released chemical diffuses to nearby cells, no synapse involved

Autocrine communication

a released chemical acts on the cell that released it

Pheromone communication

hormones between individuals of the same species

Allomone communication

hormones across species

General principles of hormone action

Hormones travel throughout the body; hormone signals can be slow; hormonal effects can be gradual and last up to weeks; hormones modulate behavior - don't usually initiate/terminate it; behavior can alter hormone release; hormone levels cycle over day, month, lifetime

Similarities between hormones and neurotransmitters

both systems synthesize, store, and release chemical signals; both use specific receptors, often with intracellular biochemical pathways; both systems can affect our behavior

Differences between hormones and neurotransmitters

neurotransmitters are released at precise synapses; hormones spread throughout body, but only act on cells with receptor for them; neural messages are rapid, and hormonal messages are slower; some chemicals can be both hormones and neurotransmitters

Hormone signaling

Hormones bind to metabotropic or nuclear receptors

peptide and amine signaling

Metabotropic; cAMP, IP3, DAG; seconds to minutes to take effect

Steroid signaling

Nuclear receptors; bind transcription factor; hours to take effect

Hypothalamus and pituitary gland

Hypothalamus: neuroendocrine cells secrete "releasing hormones" - pituitary gland: secrete tropic hormones (master gland, anterior pituitary, posterior pituitary) - endocrine glands secrete hormones targeting specific cells/organs

Posterior Pituitary Gland

Hypothalamus neurons release peptide hormones into bloodstream of the posterior pituitary gland. these same peptide hormones spread throughout the body

Anterior Pituitary Gland

Hypothalamic neurons release "releasing hormones" into media eminence blood vessels - called the hypophyseal portal system; releasing hormones are carried to the anterior pituitary --> anterior pituitary releases tropic hormones into bloodstream, tropic hormones spread throughout the body

Anterior Pituitary Gland - HPA Axis

HPA = Hypothalamus Pituitary Adrenal. The adrenal cortex/gland secretes steroids, including glucocorticoids; cortisol is a glucocorticoid hormone that prepares the body to deal with stress - increase blood glucose, promotes metabolism, suppresses inflammation

Negative feedback loops - regulation/inhibition

Detect, evaluate, and regulate hormone levels and biological effects. hormone is steadily released, and once enough released the negative feedback signal gets sent. multiple levels of hormone release, multiple levels of negative feedback

High emotional reactivity in children

shy, risk averse, exaggerated amygdala responses, greater risk for anxiety disorders

How and where are emotional responses curated?

Circuit 1 (medial forebrain bundle) and circuit 2 (limbic system)

Medial forebrain bundle

activation of the MFB supports positive emotions; brain self-stimulation studies; ventral tegmental area releases dopamine into nucleus accumbens

Negative emotion is elicited by stimulating the:

limbic system

Amygdala

anxiety, stress, fear

Patient S.M.

*developed fearlessness in childhood
--outgoing, but few good friends
--confronts risk
--low sympathetic nervous system responses

*calcium deposits in amygdala

*strong, panicky fear in response to physiological challenge
--external threats detected by amygdala
--internal threats detected by brainstem

How does the amygdala detect external threats?

Low road and high road. Central nucleus is main output of amygdala

Low road

allows for immediate responses

High road

allows for higher level cognitive processing - PFC allows for observational fear learning

Stress

perceived or anticipated threat that disrupts a person's well-being or homeostasis

Physical stress

exposure to cold temperatures, illness, etc.

Psychological stress

predators, deadlines, financial difficulties, etc.

Stress responses

physiological processes that help the individual cope with acute stress. Chronic stress may lead to adaptations of the stress response (allostasis) that may lead to pathological states

Stressors activate three physiological stress response systems:

sympathetic nervous system. HPA axis, immune system

Sympathetic nervous system

Fast, but short-lived stress response

Sympathetic nerves project from the brain to:

Target organs (heart), where norepinephrine is released; adrenal medulla --> release of epinephrine and norepinephrine into the bloodstream. Epinephrine and norepinephrine support fight-or-flight response (increased heart rate, blood pressure, respiration; increased blood delivery to muscles; mobilization of fatty acids for metabolism; in the brain, norepinephrine released at synapses increases arousal modulates cognition and emotion)

HPA Axis

Slower but more prolonged stress response. Stressors trigger the hypothalamus to release corticotropin-releasing hormone/factor (CRH/CRF). CRF triggers the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH triggers the adrenal glands to release cortisol into the bloodstream

Cortisol activates:

glucocorticoid receptors (a type of nuclear receptor), found in many tissues. Brain: increases arousal; heart: increases cardiovascular tone; immune cells: increases immune response; Liver: promotes gluconeogenesis

Immune system

Norepinephrine, epinephrine, and cortisol stimulate immune cells to release proinflammatory cytokinesis. Sympathetic nerves also directly innervate lymphoid organs --> stimulate production of cytokinesis. Cytokinesis stimulates the HPA axis and sympathetic nervous system. Chronic stress may deplete this system

Hypothalamus

communicates what the brain perceives as stressful to the body --> physiological stress responses

Autonomic (sympathetic) activation

paraventricular nucleus (PVN) and lateral hypothalamic (LH) neurons to sympathetic preganglioonic neurons in medulla and brainstem

HPA Axis activation

via the paraventricular nucleus (PVN), pituitary, and adrenals

Immune activation

indirect

How does the brain recognize psychological stressors?

upstream of the hypothalamus, the amygdala 'recognizes' stressors. amygdala neurons directly project to the hypothalamus

Amygdala inputs

sensory inputs are primarily sent through the thalamus

the amygdala receives visceral information (hunger state) through the:

hypothalamus, septal area, orbital cortex, parabrachial nucleus

Amygdala outputs

ventral amygdalofugal pathway; stria terminalis; direct projections to hippocampus, entorhinal cortex, thalamus, brainstem

Ventral Amygdalofugal Pathway

connects the amygdala with ventral striatum, cortical areas, septal area, hypothalamus. conscious perception of emotions, formation of learned associations between behaviors and emotions

Stria terminalis

connects the amygdala with hypothalamus, septal area, habenula

Direct connections in the brain

hippocampus - contextual and emotional memory; brainstem - autonomic activation

Mid life stress =

stress immunization

More significant early life stress =

greater stress response, long-lasting changes in brain, elevated baseline proinflammatory markers, increased risk for anxiety, depression, PTSD

Chronic stress and the immune system

stress activates the immune system - elevated proinflammatory leukocytes can adhere to the walls of blood vessels, forming plaques - plaques may become loose and lead to a heart attack or stroke. chronic stress weakens the function of immune cells - susceptibility to infections

Chronic stress and cortisol

chronic stress leads to chronic upregulation of cortisol release. sleep disturbance - cortisol promotes arousal; hypertension - cortisol promotes higher blood pressure; stomach ulcers - cortisol promotes gastric secretions; obesity - cortisol promotes food consumption and fat storage

Negative Affective disorders

The world is experienced in negative terms - higher levels of distress, anxiety, dissatisfaction; genetic risk; chronic, lower grade stressors increase risk for anxiety disorders or depression

General stress adaptation theory

alarm: body mobilizes to confront threat; resistance: body actively copes with threat; exhaustion: chronic perceived threat depletes the body's resources

Dysregulation of stress adaptation leads to negative affective disorders

chronic stress produces excess alarm. contribute to development of negative affective disorders

Dysregulated HPA Axis is associated with depression because:

cortisol is chronically elevated, reduced variability and adaptability, reduced stress resistance

Dexamethasone Suppression Test

Dexamethasone is a synthetic glucocorticoid which "tricks" the hypothalamus that cortisol levels are high --> feedback inhibition

Generalized anxiety disorder

chronic anxiety, exaggerated tension

Obsessive-compulsive disorder

recurrent unwanted thoughts or repetitive behavior

Panic disorder

unexpected, repeated episodes of intense fear and physical symptoms

Posttraumatic stress disorder

memories of unpleasant event produce same intense visceral arousal. Symptom clusters: avpoidance of trauma-associated stimuli, intrusion of negative recollections, negative alterations in mood and cognition, alterations in arousal and reactivity

Social anxiety disorder

overwhelming anxiety and excessive self-consciousness in everyday social situations

Model of PTSD

*original trauma activates
--1. alarm stress systems
--2. amygdala
*subsequent stressors produce heightened alarm stress response
*triggers traumatic memory (via amygdala)
*over time, traumatic memory associations and physiological response are strengthened

Schizophrenia

thought, mood, affect, and behavior are splintered

Positive symptoms of schizpohrenia

(refers to symptoms that are present but should not be) psychosis: hallucinations, delusions, disorganized thought and speech, bizarre behaviors

Negative symptoms of schizophrenia

(refers to characteristics of the individual that are absent but should be present) emotional dysregulation: lack of emotional expression, reduced facial expression, inability to experience pleasure in everyday activities; impaired motivation: reduced conversation, diminished ability to begin or sustain activities, social withdrawal

Cognitive symptoms of schizophrenia

(refers to problems with processing and acting on external information) neurocognitive impairment: memory problems, poor attention span, difficulty making plans, reduced decision-making capacity, poor social cognition, abnormal movement pattetns

What may promote psychosis?

psychotic substances (stimulant drugs of abuse, high potency cannabis and psychedelics); inflammation, injury, illness (meningitis and encephalitis, tumors, strokes, Parkinson's and Alzheimer's; stress/trauma susceptibility

Underlying neurobiology in schizophrenia

1. Ventricle volume (patients have larger ventricles)
2. Limbic system (hippocampus and amygdala are smaller in patients, disorganization of hippocampal pyramidal cells)
3. Cortex (thinning of grey matter, hypofrontality (less cortical activation). Neurobiological changes can progress and worsen

Chlorpromazine

Antipsychotic drugs, anesthetic, lessened psychosis symptoms, dramatically impaired voluntary movement, D2 receptor antagonist, L-DOPA can worsen psychosis in Parkinson's patients. D2 antagonism predicts clinical efficacy

Dopamine hypothesis

Dopamine overactivity in limbic system causes positive symptoms. dopamine function is too low in the frontal cortex and too high in limbic system

Limitations of dopamine hypothesis

not all symptoms are treated well by dopamine antagonists; not all patients will respond to a dopamine antagonist; even if they do respond, their delay to efficacy is prolonged, and the associated adverse effets are substantial