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Thalamus - the gateway to consciousness

Thalamus - the gateway to consciousness

The thalamus is not part of the HPA axis. However, together with the basal ganglia, it is the central filter and control circuit that regulates the HPA axis.

The thalamus is the “gateway to consciousness”.
The thalamus receives information from the sensory organs and from the body and transmits it to the cortex (cerebral cortex) in its specific thalamic nuclei. The thalamus works as a filter with regard to the importance of information and thus regulates which signals are passed on to the cortex, where the living being becomes aware of them. The efferent (incoming) nerve pathways are predominantly crossed, i.e. each half of the thalamus is controlled by the opposite half of the body.

The thalamus consists of sensorimotor nuclei, limbic nuclei and connection nuclei.
The most important part of the thalamus, the dorsal thalamus, is controlled by the cortex, the ventral thalamus (subthalamus) and the reticular nucleus in order to prevent overexcitation or underexcitation.
The thalamus is also involved in stress regulation. Severe stress can cause atrophy of the thalamus. Early childhood stress can change the connectivity of the thalamus and influence the addressing of the amygdala. Mice with deactivated PTCHD1 in the thalamus show, among other things, inattention, hyperactivity and impulsivity.

1. Structure and function of the thalamus

The dorsal part of the thalamus (thalamus dorsalis) and the cortex reinforce and inhibit each other, forming a feedback loop. To prevent this from leading to 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, are functionally part of the basal ganglia.

While the ventral thalamus directly and indirectly controls the dorsal thalamus, the reticular nucleus acts as a delayed brake on the thalamus. The reticular nucleus receives the same signals from the cortex as the dorsal thalamus and acts with a time delay against the effect of the cortex on the thalamus. So if the cortex activates (or inhibits) an area of the dorsal thalamus, the reticular nucleus will inhibit (or activate) precisely this part of the thalamus with a time delay.

In addition, the circuit control of the thalamus, which information goes to the cortex, is supported by the filter 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

1.1. 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)
    • Posteromedial ventral nucleus
    • It processes information from the sides of the face, further inwards from the lips and towards the center from the throat.
  • Posterior ventral nucleus
    • 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
    • Part of control loops that regulate movement sequences
  • Ventral medial nucleus (VM)

1.2. Limbic thalamic nuclei

The limbic nuclei of the thalamus are predominantly connected to 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, in particular the 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.2
        • Receives inputs from3
          • Brain stem
          • Hypothalamus
        • Addressed to3
          • MPFC
          • Nucleus accumbens
          • Amygdala
        • Serves in particular to adapt to3
          • Chronic stress
          • Addictive behavior
          • Reward
          • Mood
          • Emotion
        • Controls 3
          • Circadian timing and
          • Sleep-wake regulation
          • Connection with suprachiasmatic nucleus of the 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, in particular with the hippocampus and the mPFC, and are thus involved in their interactions.
      As filters of the information circuit between the PFC and the hippocampus, both control spatial memory 45
      • Nucleus reuniens (RE)
        • RE controls the mutual circulation of information between the hippocampus and PFC and ensures coherence between the hippocampus and PFC,65 e.g.
          • The generalization of experiences of fear7
          • The generalization of memory content in general7
          • The recall of memory content, but not the acquisition8
        • In case of stress, the RE6
          • Depressive behavioral reactions
          • Anhedonia
          • The known neuromorphological and endocrine correlates of chronic stress
        • Removing the RE prevents these reactions6
      • Rhomboid nucleus (RH)
  • Medial thalamic nuclei

    • Mediodorsal nucleus (MDm)
    • Central medial nucleus (CM) of the intralaminar complex
      MDm and CM have anatomical and functional properties that are very similar to the 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 perception of stress 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.9
Severe stress causes atrophy (death of nerve cells, tissue atrophy) in the thalamus (on both sides) and in the right visual cortex.10
The dorsal thalamus does not appear to be responsible for the reduced catecholamine release in response to acute stress in the presence of early childhood stress damage. 30 days after removal of the dorsal thalamus, rats that were repeatedly separated from their mothers as babies (which causes typical damage from early childhood chronic stress) showed lower noradrenaline blood levels and higher beta-adrenoreceptor density than rats without separation from their mothers. Early maternal separation was generally correlated with increased norepinephrine levels, which were further increased by removal of the dorsal thalamus. The noradrenaline stress response was significantly higher in securely bonded rats than in rats separated from their mothers as babies. Cardiac beta-adrenoceptors decreased even more in response to acute stress in rats separated as babies than in securely bonded rats. Removal of the dorsal thalamus further reduced cardiac beta-adrenoceptors. Activation of the sympathetic adrenal medulla by acute stress was significantly greater in securely restrained rats and correlated with downregulation of myocardial beta-adrenoceptors.11

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 the salience and default mode networks. The severity of early childhood stress experience predicted increased global connectivity of the left thalamus.12
Early childhood stress altered the addressing of the amygdala by the thalamus.13

4. Thalamus-hippocampus-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 thalamus-hippocampus-insula/midbrain circuit.14

5. Deactivated PTCHD1 receptors in the thalamus cause ADHD symptoms

Male mice with genetically deactivated PTCHD1 showed increased levels of inattention, hyperactivity and impulsivity.
More on this at PTCHD1-KO mouse In the article ADHD in an animal model

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  2. Beas, Wright, Skirzewski, Leng, Hyun, Koita, Ringelberg, Kwon, Buonanno, Penzo (2018): The locus coeruleus drives disinhibition in the midline thalamus via a dopaminergic mechanism. Nat Neurosci. 2018 Jul;21(7):963-973. doi: 10.1038/s41593-018-0167-4.

  3. Colavito, Tesoriero, Wirtu, Grassi-Zucconi, Bentivoglio (2015): Limbic thalamus and state-dependent behavior: The paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks.Neurosci Biobehav Rev. 2015 Jul;54:3-17. doi: 10.1016/j.neubiorev.2014.11.021.

  4. Layfield, Patel, Hallock, Griffin (2015): Inactivation of the nucleus reuniens/rhomboid causes a delay-dependent impairment of spatial working memory. Neurobiol Learn Mem. 2015 Nov;125:163-7. doi: 10.1016/j.nlm.2015.09.007.

  5. Hallock, Wang, Griffin (2016): Ventral Midline Thalamus Is Critical for Hippocampal-Prefrontal Synchrony and Spatial Working Memory. J Neurosci. 2016 Aug 10;36(32):8372-89. doi: 10.1523/JNEUROSCI.0991-16.2016.

  6. Kafetzopoulos, Kokras, Sotiropoulos, Oliveira, Leite-Almeida, Vasalou, Sardinha, Papadopoulou-Daifoti, Almeida, Antoniou, Sousa, Dalla (2018): The nucleus reuniens: a key node in the neurocircuitry of stress and depression. Mol Psychiatry. 2018 Mar;23(3):579-586. doi: 10.1038/mp.2017.55.

  7. Xu, Südhof (2013): A neural circuit for memory specificity and generalization. Science. 2013 Mar 15;339(6125):1290-5. doi: 10.1126/science.1229534.

  8. Davoodi, Motamedi, Akbari, Ghanbarian, Jila (2011): Effect of reversible inactivation of reuniens nucleus on memory processing in passive avoidance task. Behav Brain Res. 2011 Aug 1;221(1):1-6. doi: 10.1016/j.bbr.2011.02.020.

  9. Reinelt, Uhlig, Müller, Lauckner, Kumral, Schaare, Baczkowski, Babayan, Erbey, Roebbig, Reiter, Bae, Kratzsch, Thiery, Hendler, Villringer, Gaebler (2019): Acute psychosocial stress alters thalamic network centrality. Neuroimage. 2019 Oct 1;199:680-690. doi: 10.1016/j.neuroimage.2019.06.005.

  10. Yoshii, Oishi, Ikoma, Nishimura, Sakai, Matsuda, Yamada, Tanaka, Kawata, Narumoto, Fuk (2017): Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model. Sci Rep. 2017 Oct 6;7(1):12731. doi: 10.1038/s41598-017-12917-z.

  11. Suárez, Rivarola, Molina, Levin, Enders, Paglini (2004): The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions. Stress. 2004 Sep;7(3):195-203.

  12. Philip, Tyrka, Albright, Sweet, Almeida, Price, Carpenter (2016): Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity. J Psychiatr Res. 2016 Aug;79:93-100. doi: 10.1016/j.jpsychires.2016.05.003.

  13. Danielewicz, Hess (2016): Early life stress alters synaptic modification range in the rat lateral amygdala. Behav Brain Res. 2014 May 15;265:32-7. doi: 10.1016/j.bbr.2014.02.012.

  14. Chang, Yu (2019): Hippocampal connectivity in the aftermath of acute social stress. Neurobiol Stress. 2019 Sep 16;11:100195. doi: 10.1016/j.ynstr.2019.100195. PMID: 31832509; PMCID: PMC6889252.

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