Experimental Brain Research

, Volume 237, Issue 6, pp 1397–1407 | Cite as

c-Fos expression in the limbic thalamus following thermoregulatory and wake–sleep changes in the rat

  • Marco LuppiEmail author
  • Matteo Cerri
  • Alessia Di Cristoforo
  • Timna Hitrec
  • Daniela Dentico
  • Flavia Del Vecchio
  • Davide Martelli
  • Emanuele Perez
  • Domenico Tupone
  • Giovanni Zamboni
  • Roberto Amici
Research Article


A cellular degeneration of two thalamic nuclei belonging to the “limbic thalamus”, i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia. To better assess the physiological role of these nuclei in autonomic and sleep regulation, c-Fos expression was measured in rats during a prolonged exposure to low ambient temperature (Ta, − 10 °C) and in the first hours of the subsequent recovery period at normal laboratory Ta (25 °C). Under this protocol, the thermoregulatory and autonomic activation led to a tonic increase in waking and to a reciprocal depression in sleep occurrence, which was more evident for REM sleep. These effects were followed by a clear REM sleep rebound and by a rebound of Delta power during non-REM sleep in the following recovery period. In the anterior thalamic nuclei, c-Fos expression was (1) larger during the activity rather than the rest period in the baseline; (2) clamped at a level in-between the normal daily variation during cold exposure; (3) not significantly affected during the recovery period in comparison to the time-matched baseline. No significant changes were observed in either the MD or the paraventricular thalamic nucleus, which is also part of the limbic thalamus. The observed changes in the activity of the anterior thalamic nuclei appear, therefore, to be more specifically related to behavioral activation than to autonomic or sleep regulation.


Fatal familial insomnia Sleep deprivation Cold exposure Autonomic regulation P-CREB 



Anterodorsal thalamic nuclei


Areas of interest


Anteroventral thalamic nuclei


Control experimental condition, starting at 9 AM 24 h at n-lab Ta


Control experimental condition, starting at 9 AM 5 h at n-lab Ta


3,3′-Diaminobenzidine tetrahydrochloride


Exposure experimental condition, starting at 9 AM 24 h at − 10 °C


Exposure experimental condition, starting at 9 AM 48 h at − 10 °C


Exposure experimental condition, starting at 9 AM 5 h at − 10 °C




Fatal familial insomnia


Hue–saturation–intensity digital system


Image Pro Analyzer software


Immunoreactive neurons




Motor activity


Mediodorsal thalamic nuclei


Median preoptic nucleus of the hypothalamus

n-lab Ta

Normal laboratory ambient temperature (i.e., 25.0 ± 1.0 °C)


Non-REM sleep


Phosphorylated cAMP-response-element-binding-protein


Paraventricular thalamic nucleus


Recovery experimental condition, starting at 9 AM 5 h at n-lab Ta following 24 h at − 10 °C


Recovery experimental condition, starting at 9 AM 5 h at n-lab Ta following 48 h at − 10 °C


Rapid-eye movement


REM sleep


Ambient temperature


Hypothalamic temperature


Ventral anterior thalamic nuclei


Ventrolateral preoptic nucleus of the hypothalamus





This work has been supported by the Ministero dell’Università e della Ricerca Scientifica (MIUR), Italy and by the University of Bologna. The authors wish to thank Ms. Melissa Stott for reviewing the English.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed were in accordance with the ethical standards of the institution or practice at which the studies were conducted.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biomedical and NeuroMotor SciencesUniversity of BolognaBolognaItaly
  2. 2.University of Wisconsin-MadisonMadisonUSA
  3. 3.Institut de Recherche Biomédicale des Armées, Unité Risques Technologiques EmergentsBretigny/Orge CedexFrance
  4. 4.Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  5. 5.Department of Neurological SurgeryOregon Health and Science UniversityPortlandUSA
  6. 6.Dipartimento Interateneo di FisicaUniversità degli Studi “Aldo Moro” di BariBariItaly

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