Limbic System

Module 5: Overview of Other Important Brain Structures

General Goals:
  - Focus on functional anatomy rather than physiology.
  - Objectives include:
    1. Identifying important structures within the limbic system and cerebral cortex.
    2. Summarizing their function.
    3. Summarizing their inputs (type of information and approximate origin).
    4. Summarizing their outputs (where they send information and why).

Fast Pain vs. Slow Pain Ascending Tracts

Types of Pain:
  - Fast Pain:
    - Involves mainly Ad fibers.
  - Slow Pain:
    - Considered “emotional” pain.
    - Mainly involves C fibers and has a significant influence on the limbic system.

Limbic Nuclei Functions

Functions Related to:
- Self-preservation.
- Species-preservation.
Major Functions of the Limbic System Include:
  - Influencing the emotional state of mind and feelings associated with sensory information.
  - Regulating autonomic and endocrine responses to emotional stimuli.
  - Setting the level of arousal.
  - Motivating behaviors and reinforcing actions.
  - Critical for long-term declarative memory.
  - Direct connections to the olfactory system and indirect connections from all other sensory modalities.

Anatomical Components of the Limbic System

Original Limbic System Components (Broca, 1824-1880):
  - Cingulate gyrus.
  - Parahippocampal gyrus.
  - Hippocampal formation.
Additional Components Include:
- Insula.
- Limbic cortex.

Papez Circuit

Definition:
- “The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus, the hippocampus and their interconnections constitute a harmonious mechanism which may elaborate the functions of central emotion as well as participate in the emotional expression.” - James Papez, 1937

Expanded Limbic System

Additional Structures Include:
  - Anterior commissure.
  - Anterior nucleus of thalamus.
  - Stria medullaris.
  - Cingulate gyrus.
  - Medial forebrain bundle.
  - Septal nuclei.
  - Thalamus.
  - Corpus callosum.
  - Habenular nucleus.
  - Fornix.
  - Subcallosal area.
  - Paraterminal gyrus.
  - Olfactory tubercle.
  - Olfactory bulb.
  - Hypothalamus.
  - Rhinal sulcus.
  - Parahippocampal gyrus.
  - Longitudinal striae (Indusium griseum).
  - Stria terminalis.
  - Fimbria.
  - Fasciolar gyrus.
  - Hippocampal formation.
  - Lingual gyrus.
  - Interpeduncular nuclei.
  - Dentate gyrus.
  - Mammillothalamic tract.
  - Mammillary body.
  - Amygdaloid complex.

Basic Summary of Connections in the Limbic System

Key Functions Include:
  - Autonomic nervous system (ANS) and endocrine control.
  - Memory processing.
  - Motivation regulation.
  - Smell and emotions linkage.
  - Reward mechanisms.
  - Connections to the septal area and nucleus accumbens, and limbic cortex (including cingulate gyrus, insula, parahippocampal gyrus).

Hormonal Control by Hypothalamus

Functions:
  - Act as the autonomic and endocrine control center.
  - Receives information regarding system status from both central and peripheral nervous systems, including direct hormone level sensing.
  - Coordinates a response through autonomic nervous system and endocrine systems.

Basal Ganglia and Dopamine Pathways

Key Components:
- Substantia pars compacta.
- Dopaminergic pathways involved in reward and motivation.
Pathways Include:
  - General role of relaying information regarding motivation to different brain areas.
  - Key Pathways:
    - Nigrostriatal pathway:
      - Projects from the Substantia Nigra to striatum, influencing action selection.
    - Mesolimbic pathway:
      - Projects from the ventral tegmental area (VTA) to the nucleus accumbens (NAc).
      - Important for reward and reinforcement, with narcotics elevating dopamine levels in NAc leading to addiction.

Dopamine and Motor Control

Dopaminergic Receptors:
  - D2 Receptor:
    - Gi coupled dopamine receptor.
  - D1 Receptor:
    - Gs coupled dopamine receptor.
Pathway Roles:
- Direct, indirect, and hyperdirect pathways influence motor processes and feelings, particularly in states of hunger.

Reward and Hedonistic Responses

Coupled Effects of Rewarding Stimuli:
  - Reinforcement:
    - A direct unconscious desire to engage in activities related to the reward (“wanting”).
  - Hedonism:
    - A conscious pleasure derived from the reward (“liking”).
Mediation Mechanism:
- Largely facilitated by elevated dopamine transmission from VTA to the ventral striatum.

Pleasure Experience and Opioid Sensitivity

Pathways of Pleasure:
- Involve numerous anatomical hotspots correlated with pleasure and distaste.
- Highly sensitive to opioids, according to imaging studies (Berridge & Kringlebach, 2015).

Hippocampus and Memory

Hippocampal Amnesia Case Study: Henry Molaison

Background Information:
  - Henry Molaison (1926-2008) underwent bilateral medial temporal lobectomy to alleviate epilepsy.
  - Resulted in the removal of amygdalae and approximately half of the hippocampal formations.
  - Later discovered damage included parts of the prefrontal cortex.
Notable Results:
- Loss of long-term semantic and episodic memory but intact working memory.
- Relatively intact spatial memory influenced by the posterior hippocampus or possibly cortical remodeling.

Memory Types Associated With the Hippocampus

Types Include:
  - Explicit Memory (Conscious):
    - Names, faces, numbers, places, dates, etc.
  - Implicit Memory (Unconscious):
    - Motor learning (“muscle memory”).
Functions of Hippocampus:
  - Seat of conscious learning and memory through:
    - Spatial learning and navigation.
    - Episodic/event memory.
    - Associational recollection.

Memory Inputs Processed by the Hippocampus

Integration of Inputs:
- “What?”, “Where?”, and “When?” inputs along with “Feel?” inputs are received.
- Memories are formed based on the emotional strength associated with the experience.
Storage Areas:
- Declarative memory is chiefly stored in the hippocampus and prefrontal cortex.

Hippocampal Structure and Circuits

Hippocampal Anatomy

Regions Identified Include:
- CA2, CA1, CA3, and Dentate Gyrus (DG).
Components of the Circuit:
- Contains axons and dendrites with significant pathways (Schaffer collaterals).
- “Trisynaptic circuit” includes information from the limbic system about emotional experiences.

Long-Term Potentiation (LTP) and Long-Term Depression (LTD)

Mechanisms Include:
  - LTP:
    - High level of NMDA-mediated Ca2+ entry.
  - LTD:
    - Low level of NMDA-mediated Ca2+ entry.
Key Molecules Involved:
  - NMDA receptors (NMDAR) and AMPA receptors (AMPAR).
  - Expression Mechanisms:
    - Postsynaptic insertion of AMPARs through activation of CaMKII for LTP.
    - Internalization of AMPARs through Calcineurin for LTD.

Amygdala and Emotion

Location and Role:
  - Anteriomedial temporal lobe, dorsal to the anterior tip of the hippocampus.
  - Receives multiple direct and indirect sensory inputs including those from higher cortical areas like the prefrontal cortex.
  - Pivotal in emotion and drives, impacting responses across the limbic system.

Emotional Responses and Activation

Mechanisms of Detection:
  - Images that are not consciously perceived can produce emotional responses, measured by:
    - Increased skin conductance (sympathetic ANS response).
    - Increased amygdala activity in response to direct sensory inputs (e.g., visual).

Fear Conditioning and the Amygdala

Processes Involved: (Summarized):
- Interaction of the amygdala with sensory inputs from the visual cortex, influencing heart rate and blood pressure.
- Connective pathways facilitate rapid emotional response initiations (e.g., "Run!" responses to perceived threats).

Emotional Mimicry and Empathy

Concepts:
  - Autonomic Mimicry Mechanism:
    1. Sender and Receiver Dynamics.
  - The coupling of emotional responses between various brain areas including the hypothalamus, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), and others.
Outcomes in Physiological Responses:
- Involvement of the pituitary gland, changes in pupil size, blushing, and cardiovascular reactions, mediated by Hormonal pathways (e.g., ACTH, CRH).