Purkinje Neurons
The cells that keep us moving
Credit: Art by Sam Esquillon. Set in motion by Dr. Emanuele Petretto. Words by Dr. Agnieszka Szmitkowska. Project coordination: Dr. Masia Maksymowicz. Series Director: Dr. Radhika Patnala Sci-illustrate Endosymbiont
#Extraordinarycelltypes #sciart #lifescience #purkinjecells
The coral reef of the cerebellum
Purkinje neurons are large cells found in the brain’s cerebellum cortex. They are amongst the biggest and most complex existing neurons. These cells were discovered in 1837 by Czech physiologist Jan Evangelista Purkinje. Their cell bodies are large and flask-like, with numerous branching dendrites, and a single long axon. The massive, intricately branched, flat, dendritic trees look similar to corals on the reef. And just like in corals, connected in great reefs, that structure allows them to integrate large amounts of information and connect with many other cells (1, 2).
Complex, tight-knit community of neurons
Purkinje neurons are the primary neurons responsible for transmitting information from the cerebellum to other parts of the brain. The dendritic trees of Purkinje neurons interact with two major types of input fibres: parallel fibres and climbing fibres.
Parallel fibres are the axons of the tiny granule cells, which are another type of cerebellar neurons. They cross the coral reef of Purkinje cells at right angles, making numerous but individually weak connections. These parallel fibres are activated by sensory or motor inputs. They induce what are known as “simple spikes” in the Purkinje neurons. These spikes represent the Purkinje cells’ way of integrating a large volume of relatively weak inputs, helping to modulate fine motor movements and coordinate ongoing activities (3).
On the other hand, climbing fibres originate from a different brain region called the inferior olivary nucleus, located in the medulla oblongata. Each Purkinje neuron receives input from only one climbing fibre, in contrast to the numerous connections with the parallel fibres. This strong connection forms multiple synaptic contacts with the Purkinje cell dendrites. Activation of the climbing fibre triggers a “complex spike” in the Purkinje cell — a strong, bursting form of activity. Complex spikes are thought to be instrumental in cerebellum-dependent forms of learning and synaptic plasticity, allowing for the adaptation and fine-tuning of motor skills (4).
This extensive network allows Purkinje cells to receive up to 200,000 synaptic inputs from other neurons (5)!
Neurons of coordination
Purkinje neurons are crucial for our motor control. They integrate excitatory signals from the fibres described above and generate outputs that are inhibitory in nature. They use the neurotransmitter GABA (gamma-aminobutyric acid) to send inhibitory signals to deeper cerebellar structures like the deep cerebellar nuclei and the vestibular nuclei. The deep cerebellar nuclei act as the primary output centres of the cerebellum, sending processed information to other brain regions for the execution of motor tasks.
The vestibular nuclei are involved in balance and spatial orientation. By sending inhibitory signals to these areas, Purkinje neuronss help modulate their activity, fine-tuning the motor commands sent to the muscles. This includes activities as diverse as walking, running, and maintaining posture (gross motor skills) and more precise activities like writing, playing a musical instrument, or performing delicate surgical procedures (fine motor skills). They are also involved in the timing and execution of complex, multi-joint movements like swinging a bat or throwing a ball (6).
More than just motor skills
Although the cerebellum and its Purkinje neural circuits are most commonly associated with motor control — a fact highlighted by the presence of coordination issues like ataxia when the cerebellum is damaged without impacting muscle strength — new studies are indicating a broader role for these cells in cognitive functions (7). These include language processing and regulation of emotions such as aggression (8, 9). The mechanisms governing these newly identified functions might parallel those involved in motor tasks, likely capitalising on the cerebellum’s intrinsic neural pathways dedicated to error correction and fine-tuning. (10).
When the circuit breaks
When Purkinje neurons are lost or damaged, it can have profound neurological consequences. One well-known example is their vulnerability to alcohol exposure during embryonic development. It can lead to permanent cell loss and contribute to the symptoms of fetal alcohol syndrome (FAS). Children with FAS often exhibit a range of cognitive, motor, and behavioural impairments, including issues with balance and coordination that may be attributable to Purkinje neurons loss in the cerebellum (11).
As more recent research implicates the impact of Purkinje neurons in cognitive and emotional processing, the loss of those cells in individuals with autism might contribute to motor coordination issues and the cognitive and social deficits characteristic of the disorder (12).
Niemann-Pick disease type C is an inherited metabolic disorder characterised by the inability to metabolize lipids properly, leading to lipid accumulation within cells. The disease often affects the nervous system and can result in the loss of Purkinje neurons. Neurological symptoms in NPC may include ataxia (lack of muscle control), tremors, and cognitive decline, all of which could be tied back to Purkinje cell dysfunction or loss (13).
Recognizing and appreciating the labs working in this space:
- Department of Biophysics, Graduate School of Science, Kyoto University, https://www.sci.kyoto-u.ac.jp/en/divisions/biol/biophys
- Neuroscience Institute Cavalieri Ottolenghi (NICO) and Department of Neuroscience, University of Torino, Torino, Italy, https://www.nico.ottolenghi.unito.it/eng
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy, https://dbbs.dip.unipv.it/en
- Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Science, Amsterdam, the Netherlands, https://nin.nl/
- Department of Neurology, University of Michigan, USA, https://medicine.umich.edu/dept/neurology
- Department of Neurobiology, Harvard Medical School, USA, https://neuro.hms.harvard.edu/
- Department of Pathology and Immunology, Department of Neuroscience, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, Houston, Texas, https://nri.texaschildrens.org/
- Depts. of Otolaryngology, Neuroscience & Physiology, and the Neuroscience Institute, NYU Grossman School of Medicine, New York, USA, https://med.nyu.edu/departments-institutes/neuroscience-physiology/
- Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands, https://neuro.nl/
- Davee Department of Neurology and Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA, https://www.neurology.northwestern.edu/index.html
References:
1. Hirano T. Purkinje neurons: development, morphology, and function. The Cerebellum. 2018;17(6):699–700.
2. Goodlett CR, Mittleman G. Chapter 9 — The Cerebellum. In: Conn PM, editor. Conn’s Translational Neuroscience. San Diego: Academic Press; 2017. p. 191–212.
3. Hoxha E, Tempia F, Lippiello P, Miniaci MC. Modulation, Plasticity and Pathophysiology of the Parallel Fiber-Purkinje Cell Synapse. Frontiers in Synaptic Neuroscience. 2016;8.
4. Schmolesky MT, De Zeeuw CI, Hansel C. Climbing fiber synaptic plasticity and modifications in Purkinje cell excitability. Progress in Brain Research. 148: Elsevier; 2005. p. 81–94.
5. Masoli S, D’Angelo E. Synaptic Activation of a Detailed Purkinje Cell Model Predicts Voltage-Dependent Control of Burst-Pause Responses in Active Dendrites. Frontiers in cellular neuroscience. 2017;11:278.
6. Medina JF. The multiple roles of Purkinje cells in sensori-motor calibration: to predict, teach and command. Curr Opin Neurobiol. 2011;21(4):616–22.
7. Chopra R, Shakkottai VG. Translating cerebellar Purkinje neuron physiology to progress in dominantly inherited ataxia. Future neurology. 2014;9(2):187–96.
8. Ciapponi C, Li Y, Osorio Becerra DA, Rodarie D, Casellato C, Mapelli L, et al. Variations on the theme: focus on cerebellum and emotional processing. Frontiers in Systems Neuroscience. 2023;17.
9. Jackman SL, Chen CH, Offermann HL, Drew IR, Harrison BM, Bowman AM, et al. Cerebellar Purkinje cell activity modulates aggressive behavior. Elife. 2020;9.
10. Paul MS, Limaiem F. Histology, Purkinje Cells. 2019.
11. Servais L, Hourez R, Bearzatto B, Gall D, Schiffmann SN, Cheron G. Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome. Proc Natl Acad Sci U S A. 2007;104(23):9858–63.
12. Sudarov A. Defining the role of cerebellar Purkinje cells in autism spectrum disorders. Cerebellum (London, England). 2013;12(6):950–5.
13. Sarna JR, Larouche M, Marzban H, Sillitoe RV, Rancourt DE, Hawkes R. Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease. The Journal of comparative neurology. 2003;456(3):279–91.
About the author:
DR. AGA SZMITKOWSKA
Content Editor The League of Extraordinary Celltypes, Sci-Illustrate Stories
Aga did her Ph.D. in Biochemistry at the CEITEC/Masaryk University in Brno, Czech Republic, where she was a part of the Laboratory of Genomics and Proteomics of Plant Systems. She is a passionate public speaker and science communicator. After graduation, she became a freelance content coordinator and strategist in a start-up environment focused on lifestyle and longevity.
About the artist:
SAM ESQUILLON
Contributing Artist The League of Extraordinary Celltypes, Sci-Illustrate Stories
Sam worked for a couple of educational children’s shows as an illustrator, puppeteer, art director, and production designer. He still works as a production designer for international films and tv/ online streaming shows.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Celltypes, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behaviour of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualisation, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series: The League of Extraordinary Celltypes
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types that make our bodies tick ❤.
