Study Guide 8: Neuromodulation and Circadian Rhythm

Neuromodulation

Diffuse Modulatory Systems

Diffuse modulatory systems consist of networks of neuromodulators that influence the excitability of the central nervous system (CNS) and brain through a method known as volume transmission. These systems originate from specific areas in the brain and have extensive influence across the CNS. The efficacy of a neuromodulator depends on the type of receptors present in a region, as they can modify the threshold for excitatory or inhibitory responses.

Four Major Systems:

1. Norepinephrine:

   • Source: Locus coeruleus

   • Projections: Widespread throughout the brain including the cortex, hippocampus, and cerebellum.

   • Features: Involved in arousal, attention, learning, memory, anxiety, mood, and metabolic regulation.

2. Serotonin:

   • Source: Raphe nuclei

   • Projections: Diffuse projections to various regions such as the limbic system and cerebral cortex.

   • Features: Involved in mood regulation, sleep/wake cycles, and overall arousal.

3. Dopamine:

   • Source: Substantia nigra and ventral tegmental area

   • Projections: Targets areas including the basal ganglia and prefrontal cortex.

   • Features: Controls voluntary movement, regulates mood, and is integral to the reward pathway.

4. Acetylcholine:

   • Source: Basal forebrain and brainstem

   • Projections: Widespread influence including the cortex and hippocampus.

   • Features: Plays a role in arousal, attention, learning, and memory, and is notably affected in Alzheimer’s disease.

Activation Behaviors Associated with Neuromodulatory Systems

• Norepinephrine: Enhances alertness and speeds up processing of information.

• Serotonin: Promotes mood stabilization and has a role in sleep regulation.

• Dopamine: Associated with movement control and reward-based behaviors.

• Acetylcholine: Implicated in cognitive functions, though its role requires further understanding.

Drug Effects and Side Effects

Drugs targeting these neuromodulatory systems can cause numerous side effects due to the diverse range of receptors these modulators interact with throughout the brain and body. Many drugs unintentionally affect multiple receptors, leading to unwanted effects and complex neuronal interactions. Understanding these systems is essential to improve drug specificity and minimize side effects.

Circadian Rhythms

Generation and Entrainment of Circadian Rhythms

Circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), which serves as the body's master clock. This regulation is partially driven by specific molecular mechanisms, including the CLOCK and BMAL1 proteins, although fully understanding these mechanisms and their influence on action potentials is an ongoing area of study.

Role of Photoreceptors in Circadian Rhythms

• Rods and Cones: Primarily responsible for vision, but do not adequately respond to light cues for circadian regulation.

• Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs): These cells directly influence the SCN by transmitting light information, thus entraining the circadian rhythm even in the absence of rod and cone function.

Sensitivity of SCN Neurons

SCN neurons likely exhibit sensitivity to body temperature or have strong connections with adjacent thermosensitive neurons, permitting them to adjust circadian rhythms in response to temperature changes, which is critical for maintaining overall bodily functions.

Impact of Lighting on Night-Shift Workers

Using dim light in workplaces for night-shift workers may hinder their ability to adapt their circadian rhythms. Dim lighting activates ipRGCs, but not sufficiently to fully entrain the SCN, thus failing to adequately shift the workers’ biological clocks.

Consequences of Poor Circadian Adaptation

Poor adaptation to night shifts may lead to disturbances in various bodily systems regulated by the SCN, including immune, endocrine, and autonomic systems. Shift workers often struggle to maintain regular eating and exercise routines due to societal norms, which further complicates circadian rhythm adjustments.

Recommendations for Shift Scheduling

For optimal worker performance, block scheduling patterns (1-2 months per shift) are advisable over weekly shift changes. This approach allows adequate time for the SCN to adjust without frequent disruptions, leading to better sleep quality and personal well-being.

Sleep

EEG Patterns in Different Sleep Stages

EEG patterns during sleep reflect the collective electrical activity of neuron groups:

• Stage 1: Characterized by theta waves.

• Stage 2: Involves sleep spindles and K-complexes.

• Stage 3: Dominated by delta waves.

Each sleep cycle lasts approximately 90 minutes with increasing proportions of REM sleep as the night progresses.

Melatonin and Sleep Induction

Melatonin, produced by the pineal gland, plays a significant role in regulating sleep cycles by decreasing SCN activity, especially useful when adjusting to new time zones. Supplementing with melatonin can facilitate sleep onset during transition periods, such as jet lag.

Importance of Sleep Hygiene

It is crucial to eliminate light exposure, particularly blue light, which activates ipRGCs and thereby influences the SCN. Following recommendations to darken sleep environments and reduce screen time prior to bed can significantly improve sleep quality by promoting natural melatonin production and allowing the SCN to function optimally during rest periods.