Neuro Week 11-1

Thalamus & Hypothalamus

Organization of motor systems

Due to complexity of movement the motor systems forms a network of hierarchically organized feedback loops

Thalamus

• Important processing station in the center of the brain

• Nearly all pathways that project to the cerebral cortex via synaptic relays in the thalamus

Thalamus functions

• Sensory relay to somatosensory cortex

• Motor relay from the cerebellum and basal ganglia to the cortex

• Limbic inputs

  • Behavior, arousal, and sleep wake cycles

The thalamus is divided into three nuclear groups

1. Medial nuclear group

2. Lateral nuclear group

3. Anterior nuclear group

   • Each group contains nuclei which project to different regions of the cortex

The three thalamus groups are divided by the

• Internal medullary which also has nuclei that project

  • Over 16 regions with nuclei that project to different regions of the cortex (don’t memorize all)

Thalamus sensory

• Thalamus = central hub for sensory processing in the brain

• Nearly all sensory information (except for olfaction) passes through the thalamus before being relayed to the cerebral cortex

• By integrating, filtering, and prioritizing sensory inputs, the thalamus ensures that the brain processes relevant information efficiently

Sensory nuclei of the thalamus

• Ventral posterior lateral (VPL) nucleus

• Ventral posterior medial (VPM) nucleus

• Lateral geniculate nucleus (LGN)

• Medial geniculate nucleus (MGN)

• Pulvinar nucleus

Ventral posterior lateral (VPL) nucleus

Processes somatosensory information from the body

Ventral posterior medial (VPM) nucleus

Processes somatosensory information from the face

Lateral geniculate nucleus (LGN)

Relays visual information

Medial geniculate nucleus (MGN)

Relays auditory information

Pulvinar nucleus

Integrates higher-order sensory information and connects to association cortices

Thalamus somatosensory pathway

• Signals from the body travel through the spinothalamic tract (pain & temperature) and dorsal column-medial lemniscus pathway (touch & proprioception) to the VPL nucleus

• Signals from the face travel through the trigeminal-thalamic tract to the VPM nucleus

• Thalamus relays this information to primary somatosensory cortex (S1) in the parietal lobe

Thalamus somatosensory pathway function

Ensures accurate localization and intensity discrimination of tactile, proprioceptive, and nociceptive stimuli

Thalamus visual pathway

• Signals from the retina travel via the optic nerve, through the optic tract, and terminate in the LGN

• LGN sends visual information to the primary visual cortex (V1) in the occipital lobe

Thalamus visual pathway function

Relays color information, processing of shape motion and depth

Thalamus auditory pathway

• Signal from the cochlea travel through the inferior colliculus and terminate in the MGN

• MGN transmits auditory information to the primary auditory cortex (A1) in the temporal lobe

Thalamus auditory pathway function

Processes sound frequencies, timing, and localization

Thalamus integration and filtering

• Pulvinar nucleus connects to sensory association cortices, integrating inputs from multiple modalities (e.g., vision and touch)

• Thalamus uses descending inputs from the cortex to filter and prioritize sensory information, preventing sensory overload

Thalamic projections—relay

Thalamic lesions

• Damage to sensory nuclei (e.g., VPL or VPM) can lead to sensory deficits, such as:

  • Loss of tactile sensation

  • Impaired proprioception

  • Abnormal pain perception (e.g., thalamic pain syndrome)

Thalamic pain syndrome

• Following a thalamic stroke, patients may experience chronic pain due to disrupted pain modulation pathways

• This condition is characterized by severe, burning pain with heightened sensitivity to non-painful stimuli

Sensory integration disorders

Disruptions in the pulvinar nucleus or geniculate can lead to difficulties in sensory integration, impacting vision, hearing, or spatial awareness

Sensory integration disorders —ADHD

• There is growing evidence that thalamic dysfunction may play a role in the condition’s characteristic symptoms, such as inattention, impulsivity, and hyperactivity

• Dysfunction in this relay system can lead to difficulties in sustaining attention and managing sensory overload

• Cortico-thalamic loop is responsible for

  • Sustained attention

  • Task switching

  • Impulse control

• Sensory gating

  • Thalamus regulates sensory gating = the ability to filter out unnecessary sensory stimuli

Some people with ADHD have

• Smaller thalamic volume

• Altered communication between the BG or prefrontal cortex

Motor

• The thalamus plays crucial role in motor function by acting as a relay center

  • Basal ganglia

  • Cerebellum

  • Motor cortex

• It integrates motor and ensures:

  • Smooth

  • Coordinated movement

Motor nuclei of the thalamus

• Ventral anterior (VA)

• Ventral lateral (VL)

• These nuclei relay motor information and influence motor planning, coordination, and execution

Basal ganglia-thalamocortical loop

• BG = process motor signals related to the initiation and inhibition of movement

• Processed signals are sent from the globus pallidus (internal segment) and substantia nigra pars reticulata to the VA and VL nuclei of the thalamus

• Thalamus relays information to the primary motor cortex (M1) and premotor cortex to modulate voluntary movement

Basal ganglia-thalamocortical loop function

• Enhances motor planning and smooth execution

• Filters and selects motor signals to ensure only the most appropriate movement is executed

Cerebellar-thalamocortical loop

• The cerebellum sends output to the VL nucleus to the thalamus via the dentatothalamic tract

• Thalamus relays signals to motor cortex for adjustments to ongoing movements

Cerebellar-thalamocortical loop function

• Coordinates precise, timed movements

• Corrects movement errors during execution

Corticospinal influence

• Thalamus ensures motor signals sent from the motor cortex to the spinal cord are modulated and refined by BG and cerebellar input

• Integration prevents excessive or insufficient motor output, enabling fluid motion

Thalamic projections—relay

Thalamic lesions leads to

Damage to motor nuclei (e.g., VA or VL) can lead to motor deficits such as tremors, dystonia, or impaired coordination

Parkinson’s

Overactivity in BG pathways due to dopamine loss alters thalamic relay, leading to bradykinesia and rigidity

Cerebellar disorders

Disruption of the cerebellar-thalamic loop causes ataxia and loss of movement precision

Limbic system and thalamus

Thalamus contributions to the limbic system

• Emotional processing

• Memory formation

• Motivation and reward

• Social and cognitive function

• Arousal and attention

Emotional processing

• Thalamus integrates emotional signals from the amygdala and hypothalamus with sensory information

• Mediodorsal nucleus plays a critical role in assessing the emotional significance of the stimuli and modulating behavioral responses

Memory formation

• Anterior nucleus is central to the Papez circuit, which supports episodic memory consolidation by linking the hippocampus, mammillary bodies, and cingulate cortex

• Damage to this pathway can lead to memory deficits = anterograde amnesia

Motivation and reward

• Thalamus relays motivational signals from the limbic system to the prefrontal cortex, influencing goal-directed behavior

• Integrates sensory cues with emotional salience, which is critical for reward processing

Social and cognitive

• Mediodorsal nucleus contributes to understanding social cues, regulating emotions, and managing complex decision-making

• Dysfunction in this region is associated with conditions like schizophrenia and autism spectrum disorder (ASD)

Arousal and attention

• Thalamus helps regulate arousal and alertness, particularly through its interactions with the reticular formation and limbic structures

• These functions are critical for focusing attention on emotionally significant stimuli

Thalamic projections—limbic

Thalamic lesions are associated with

• Memory impairment (e.g., amnesia)

• Emotional dysregulation (apathy or inappropriate emotional responses

• Schizophrenia

• Anxiety and depression

• PTSD

Schizophrenia

Abnormalities in the mediodorsal nucleus and its connections to the prefrontal cortex contribute to emotional flatness, social withdrawal, and impaired decision-making

Anxiety and depression

Dysfunctional thalamic-limbic circuits may amplify negative emotional states and disrupt normal coping mechanisms

PTSD

Thalamus may fail to filter and modulate sensory inputs, leading to sensory overload and hypervigilance in individuals with post-traumatic stress disorder

Thalamus and GLP-1

• Ozempic (semaglutide), a GLP-1 receptor agonist, primarily targets the endocrine and metabolic systems

• Indirect effects on brain structures like thalamus

• Effects arise from the drug’s ability to influence neurotransmitter systems, appetite regulation, and reward processing

GLP-1 receptors in the brain—reward

• Thalamus in coordination with hypothalamus and mesolimbic reward system, processes signals related to hunger and food intake

• Ozempic’s action on GLP-1 receptors dampens these signals, reducing the drive to consume food by:

  • Altering thalamic inputs that prioritize hunger-related cues

  • Reducing food reward salience in higher cortical areas

GLP-1 receptors in the brain—energy homeostasis

• Thalamus relays metabolic sensory information from the body to the cortex

  • Ozempic modulates this relay to reduce hyperactive hunger signaling, contributing to its effects on weight loss

GLP-1 receptors in the brain—cognitive effects

• By influencing neurotransmitter systems, including dopamine and serotonin

  • Ozempic may have subtle effects on mood and decision-making related to eating behaviors

  • Thalamus plays a role in these processes by integrating emotional and sensory inputs

Vision

Hearing

Hypothalamus

• Lies anterior and inferior to the thalamus and superior to the brainstem

• Small area, however, it does A LOT

  • Influences

    • Behavior

    • Homeostasis

    • Sexual behaviors

    • Circadian rhythm

    • Emotional response

Preoptic region

• Location: anterior-most part of the hypothalamus

• Nuclei:

  • Medial preoptic nucleus

    • Regulates reproductive behaviors and gonadotropin release

    • Plays a role in thermoregulation (e.g., initiating heat loss mechanisms)

  • Lateral preoptic nucleus

    • Associated with sleep regulation and arousal

Preoptic region key functions

• Thermoregulation

• Reproductive function

• Sleep-wake cycle modulation

Anterior (supraoptic) region

• Location: just above the optic chiasm

• Nuclei

  • Supraoptic nucleus

  • Paraventricular nucleus

  • Suprachiasmatic nucleus

  • Anterior hypothalamic nucleus

  • Lateral hypothalamic area

Supraoptic nucleus

Produces vasopressin (antidiuretic hormone, ADH) and oxytocin

Paraventricular nucleus

Produces vasopressin, oxytocin, and corticotropin-releasing hormone (CRH), which regulates the stress response

Suprachiasmatic nucleus (SCN)

Acts as the body’s primary circadian clock, regulating the sleep-wake cycle and other circadian rhythms

Anterior hypothalamic nucleus

Controls heat dissipation and regulates parasympathetic functions

Lateral hypothalamic area

Promotes feeding behavior and wakefulness

Anterior (supraoptic) region key functions

• Hormone production (ADH, oxytocin)

• Circadian rhythm regulation

• Heat dissipation

• Hunger and wakefulness

Middle (tuberal) region

• Location: surrounds the tuber cinereum and lies above the median eminence

• Nuclei

  • Ventromedial nucleus

  • Dorsomedial nucleus

  • Arcuate nucleus

Ventromedial nucleus (VMN)

• Satiety center; inhibits hunger when stimulated

• Involved in aggression and defensive behaviors

Dorsomedial nucleus (DMN)

Regulates such as feeding, drinking, and body weight

Arcuate nucleus

• Produces releasing and inhibitory hormones that regulate anterior pituitary function (e.g., growth hormone-releasing hormone, dopamine)

• Plays a role in appetite control via neuropeptides like ghrelin and leptin

Middle (tuberal) region key functions

• Appetite regulation

• Pituitary hormone control

• Emotional responses and aggression

Posterior (mammillary) region

• Location: most posterior part of the hypothalamus, near the mammillary bodies

• Nuclei

  • Mammillary bodies

  • Posterior hypothalamic nucleus

Mammillary bodies

Important for memory consolidation, particularly spatial and episodic memory

Posterior hypothalamic nucleus

Regulates heat conservation and sympathetic nervous system activity

Posterior (mammillary) region key functions

• Memory processing (via connections to the limbic system)

• Heat conservation

• Sympathetic nervous system activation

Hypothalamus lesions

• Preoptic = damage can result in thermoregulatory disorders or infertility

• Anterior = may disrupt circadian rhythms, diabetes or body temperature regulation

• Middle = damage to VMN may lead to obesity, while arcuate nucleus dysfunction can impair hormonal balance

• Posterior= memory deficits (e.g., mammillary body damage in Wernicke-Korsakoff syndrome) or impaired sympathetic responses

Suprachiasmatic nucleus

Ventromedial nucleus