The thalamus is not part of the HPA axis. However, together with the basal ganglia, it is the central filter and regulatory circuit that controls the HPA axis.
The thalamus is the “gateway to consciousness”.
The thalamus receives information from the sensory organs and from the body and switches these on to the cortex (cerebral cortex) in its specific thalamic nuclei. In this process, the thalamus works as a filter in terms of the importance of information and thereby regulates which signals are passed on to the cortex, where they become conscious to the living being. The efferent (incoming) neural pathways are predominantly crossed, meaning that each half of the thalamus is controlled by the opposite half of the body.
1. Structure and function of the thalamus¶
The dorsal part of the thalamus (thalamus dorsalis) and the cortex reinforce and inhibit each other, thus forming a feedback loop. To prevent this from resulting in overexcitation or underexcitation, the dorsal thalamus is controlled by the ventral thalamus (subthalamus) and the reticular nucleus (reticular thalamic nucleus). Parts of the ventral thalamus, the subthalamic nucleus and the globus pallidus, functionally belong to the basal ganglia.
While the ventral thalamus controls the dorsal thalamus indirectly and directly, the reticular nucleus acts as a time-delayed brake on the thalamus. For this purpose, the nucleus reticularis receives the same signals from the cortex as the thalamus dorsalis and acts in a time-delayed manner to counteract the effect of the cortex on the thalamus. Thus, if the cortex activates (or inhibits) an area of the thalamus dorsalis, the nucleus reticularis will inhibit (or activate) exactly this part of the thalamus with a time delay.
In addition, the thalamus’ circuit control of what information goes to the cortex is supported by the filtering function of the basal ganglia. ⇒ Basal ganglia
The thalamus has three main groups: the sensorimotor nuclei, the limbic nuclei, and the area connecting these nuclei.
1.1. Sensorimotor thalamic nuclei¶
These are the main or relay nuclei of the thalamus.
-
Lateral geniculate nucleus (LGN)
-
Medial geniculate nucleus (MGN)
-
Ventral posteromedial nucleus (VPM)
- Nucleus ventralis posteromedialis
- It processes information laterally from the face, further inward that of the lips, and toward the center that of the throat.
- Nucleus ventralis posterior
- Part of the system that mediates the sense of touch and pain (somatosensory system)
- Posterolateral nucleus (VPL)
-
Posterior nucleus (PO)
-
Ventral lateral nucleus (VL)
-
Ventral anterior nucleus (VA)
- Nucleus ventralis anterolateralis
- Component of control loops that regulate motion sequences
-
Ventral medial nucleus (VM)
1.2. Limbic thalamic nuclei¶
The limbic nuclei of the thalamus are predominantly associated with limbic-related structures and play a direct role in limbic-related functions.
-
Anterior (front) core
-
Midline thalamic nuclei
-
Dorsal (posterior)
PV and PT mainly address limbic subcortical structures, especially amygdala and nucleus accumbens. They are therefore significantly involved in affective behaviors such as stress, anxiety, feeding behavior or drug seeking
- Paraventricular (PV) thalamic nucleus
- Main nucleus of the midline thalamus
- Receives GABAergic afferents from a variety of brain regions outside the thalamus, including the zona incerta, the hypothalamus, and the formatio reticularis pontis.
- Receives inputs from
- Addresses
-
MPFC
-
Nucleus accumbens
-
Amygdala
- Serves in particular to adapt to
-
Chronic stress
- Addictive behavior
- Reward
- Mood
- Emotion
- Controls
- Circadian timing and
- Sleep-wake regulation
through
- Connection with suprachiasmatic nucleus of hypothalamus
- Direct and indirect photic input
- Has wakefulness-related Fos expression that is suppressed by sleep
- Shows intrinsic neuronal properties with diurnal oscillation
- Paratenial nucleus (PT)
-
Ventral
RE and RH communicate primarily with limbic cortical structures, particularly the hippocampus and mPFC, and are thus involved in their interactions.
Both control spatial memory as filters of the information circuit between PFC and hippocampus
- Nucleus reuniens (RE)
- RE controls the mutual information circuit between the hippocampus and PFC and ensures coherence between the hippocampus and PFC, , e.g.
- The generalization of fear experiences
- The generalizations of memory contents in general
- The retrieval of memory contents, but not the acquisition
- In the event of stress, the RE conveys
- Depressive behavioral reactions
- Anhedonia
- The known neuromorphological and endocrine correlates of chronic stress
- Removal of the RE stops these reactions
- Nucleus rhomboide (RH)
-
Medial thalamic nuclei
- Mediodorsal nucleus (MDm)
- Central medial core (CM) of the intralaminar complex
MDm and CM have anatomical and functional properties very similar to midline nuclei. Therefore, the nuclei that gather dorsoventrally along the midline of the thalamus form the nucleus of the “limbic thalamus”.
1.3. The thalamic nuclei connecting the sensorimotor and limbic thalamic nuclei¶
2. Thalamus and stress regulation¶
The thalamus is centrally integrated into stress regulation.
The subjective stress sensation triggered by psychosocial stress correlates very strongly with activation of the thalamus. In contrast, thalamic activation correlated only weakly with the increase in cortisol levels.
Severe stress causes atrophy (neuronal cell death, tissue loss) in the thalamus (bilaterally) and in the right visual cortex.
The dorsal thalamus does not appear to be responsible for the decreased catecholamine release in response to acute stress in the presence of existing early childhood stress damage. thirty days after removal of the dorsal thalamus, rats repeatedly separated from their mothers as babies (causing typical damage from early childhood chronic stress) showed lower norepinephrine blood levels and higher beta-adrenoreceptor density than rats without separation from mothers. Early separation from mothers was fundamentally correlated with increased norepinephrine levels, which increased further with removal of the dorsal thalamus. The norepinephrine stress response was significantly higher in securely attached rats than in rats separated from their mothers as babies. Cardiac beta-adrenoceptors decreased even more in response to acute stress in rates separated as babies than in rats securely bound. Removal of the dorsal thalamus further decreased cardiac beta-adrenoceptors. Activation of the sympathetic adrenal medulla by acute stress was significantly greater in securely bound rats and correlated with downregulation of myocardial beta-adrenoceptors.
3. Early childhood stress and connectivity of the thalamus¶
Early childhood stress alters the connectivity of the thalamus.
The spatial distribution of global connectivity is highest in the regions of salience and default mode networks. Severity of early childhood stress experience predicted increased global connectivity of the left thalamus.
Early childhood stress altered the addressing of the amygdala by the thalamus.
4. Deactivated PTCHD1 receptors in the thalamus cause inattention and hyperactivity¶
Male mice with genetically deactivated PTCHD1 showed increased levels of
- Distractibility
- Recognition memory problems
- Atomoxetine eliminated this change.
- Hyperactivity
- Atomoxetine eliminated this change.
-
Impulsivity
- Atomoxetine eliminated this change.
- Learning Disabilities
- Hypotension
- Aggression
- Sleep fragmentation
In addition, changes in kynurenine metabolism were evident.
When PTCHD1 was deactivated only in the reticular nucleus of the thalamus, only increased levels of
- Distractibility
- Hyperactivity
- Sleep problems
5. Thalamic-hippocampal insula network and stress¶
Social stress apparently alters resting-state connectivity to and from hippocampal subregions. Stress thus alters the flow of information in the thalamic-hippocampal insula/midbrain circuit.
