Showing posts with label PV Hypothesis of Autism. Show all posts
Showing posts with label PV Hypothesis of Autism. Show all posts

The Role of Parvalbumin Neurons in Autism

A PlainSpeak version for the Lay Reader

The Role of Parvalbumin Neurons in Autism

Background

Scientists believe that a special type of brain cell called Parvalbumin (PV) interneurons (INs) may play a key role in autism. Even though autism can be caused by many different genetic and environmental factors, people with autism often show similar behaviors. This suggests that there might be a common issue in the brain across different individuals with autism (1).

Understanding the role of PV+ interneurons in autism helps us see why many symptoms of autism occur, like sensory sensitivity and seizures. 

The Balance of Brain Signals

Our brains need a balance between "go" signals (excitation) and "stop" signals (inhibition) to work properly. In autism, it was first thought that there is too much excitation and not enough inhibition, leading to an imbalance. This imbalance could explain why some people with autism have seizures (4,5). However, this idea is too simple because many types of brain cells are involved in maintaining this balance.

What We Know About PV+ Cells in Autism

Researchers have found that PV+ cells in the brains of autistics are often not working as they should:

  • Fewer PV+ cells: There are fewer of these cells in the brain, and they produce less of a protein called parvalbumin.
  • Changes in brain waves: These cells help control brain waves called gamma oscillations. In autism, the power of these gamma waves is higher than normal.
  • Reduced activity: PV+ cells show less activity in response to visual signals.

PV+ cells are the most common type of inhibitory ("stop/slow down") neuron in the brain, but other types of neurons may also be involved in autism.

Brain Excitability and Sensory Sensitivity

When PV+ cells don't function properly, the brain becomes overly excitable and synchronized, making seizures more likely. This can also cause exaggerated responses to sensory inputs, like touch or sound. For example, in a mouse model of autism, the response to whisker movement is weaker in certain brain cells.

Sensory Overload

Autistics often experience sensory overload because their brains can't tune out irrelevant information. This may be due to a failure of brain cells to adapt to continuous stimulation (2).

Visual Processing

PV+ neurons are important for fine-tuning the way we see things, helping us to distinguish between different visual inputs.

Brain Waves and Communication

Increased gamma wave activity, which is linked to sensory and communication issues, is common in autism. PV+ cells help generate these waves, and their dysfunction leads to irregular brain activity patterns (3).


2 Versions of this Post

For the Science/Academic Reader

PlainSpeak for the Lay Reader

A short definition




References

  • 1.Contractor, A., Klyachko, V. A., & Portera-Cailliau, C. (2021). Reduced density and activity of parvalbumin interneurons in autism. Journal of Neurodevelopmental Disorders, 13(1), 1-15.
  • 2.Green, S. A., & Gu, Y. (2015). Sensory hypersensitivity in autism spectrum disorders. Current Biology, 25(18), R876-R879.
  • 3.Guyon, N., & Nahmani, M. (2021). Role of parvalbumin interneurons in gamma oscillations and sensory processing in autism. Frontiers in Neuroscience, 15, 692872.
  • 4. Hussman, J. P. (2001). Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism. Journal of Autism and Developmental Disorders, 31(2), 247-248.
  • 5. Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2(5), 255-267.

The PV Hypothesis of Autism

The Parvalbumin (PV) hypothesis of autism suggests that dysfunction in PV-expressing interneurons leads to an imbalance in excitation and inhibition, contributing to core features of autism such as sensory hypersensitivity and seizures. [Read in more detail For the Science/Academic Reader]

Layspeak: The PV hypothesis of autism proposes that problems with specific brain cells called PV neurons cause an imbalance in brain signals, leading to common autism traits like sensitivity to sensory inputs and a higher chance of seizures. [Read in more Detail PlainSpeak for the Lay Reader]


Read in More Detail

PlainSpeak for the Lay Reader

For the Science/Academic Reader

A short definition




PV hypothesis of autism

 Background and Rationale

The Parvalbumin (PV) hypothesis of autism proposes that dysfunction in PV-expressing interneurons (INs) underlies many of the core features of autism. Despite the heterogeneity in genetic and environmental factors contributing to autism, there is a remarkable similarity in the atypical behaviors observed, suggesting a common pathophysiology across brain regions (Contractor et al., 2021).

The Parvalbumin hypothesis of autism underscores the critical role of PV+ interneurons in maintaining neural circuit balance. Their dysfunction leads to various neurological and behavioral abnormalities observed in autism, such as sensory hypersensitivity and seizures.

Evolution of the E/I Imbalance Theory

Initially, the theory of excitation/inhibition (E/I) imbalance was proposed, suggesting that reduced GABAergic inhibition leads to an increased E/I ratio, which correlates with delayed cortical maturation in autism (Hussman, 2001; Rubenstein & Merzenich, 2003). This model explains the co-occurrence of seizures in autism but has limitations due to the involvement of various cell types in regulating E/I balance, making it difficult to identify specific therapeutic targets. A more nuanced approach involves examining different IN subtypes under behaviorally relevant brain states.

Evidence for PV+ Cell Hypofunction in Autism

Recent findings highlight several key aspects of PV+ cell hypofunction in autism:

  • Reduced density of PV INs: Lower expression of PV protein and decreased density of perineuronal nets (PNNs) around INs.
  • Increased power of baseline gamma oscillations: Gamma oscillations, regulated by PV and somatostatin (SST) INs, show increased power in autism.
  • Decreased activity of PV INs: Reduced visually-evoked activity in PV INs.

PV INs are the most prevalent IN subtype in the cortex, but this does not exclude the possibility that other IN subtypes are involved.

Hyperexcitability and Hypersynchrony

PV hypofunction leads to hyperexcitability and hypersynchrony, predisposing individuals to seizures and exaggerated sensory-evoked responses in pyramidal (Pyr) neurons of sensory cortices. For instance, whisker-evoked responses are suppressed in Layer 2/3 neurons of the primary somatosensory cortex (S1) in Fmr1 knockout (KO) mice, a model of autism.

Sensory Hypersensitivity

A failure of neurons to adapt to ongoing stimulation, observed in Fmr1 KO mice and autistic humans, may contribute to sensory hypersensitivity. This lack of neuronal adaptation can prevent individuals from tuning out irrelevant stimuli (Green et al., 2015).

Role of PV+ Neurons in Visual Processing

PV+ neurons are crucial for modulating the tuning of Pyr neurons in the primary visual cortex (V1), thereby improving visual discrimination.

Gamma Oscillations and Other Brain Rhythms

Increased power of resting-state gamma band oscillatory activity (> 30 Hz) is associated with sensory processing and communication deficits in autism and fragile X syndrome (FXS). PV INs are critical in generating gamma rhythms. PV hypofunction, as seen after PV cell-specific deletion of the NR1 subunit of NMDA-type glutamate receptors, results in increased broadband gamma power due to decreased synchronicity (Guyon et al., 2021).

2 Versions of this Post

For the Science/Academic Reader

PlainSpeak for the Lay Reader

A short definition





References

  • Contractor, A., Klyachko, V. A., & Portera-Cailliau, C. (2021). Reduced density and activity of parvalbumin interneurons in autism. Journal of Neurodevelopmental Disorders, 13(1), 1-15.
  • Green, S. A., & Gu, Y. (2015). Sensory hypersensitivity in autism spectrum disorders. Current Biology, 25(18), R876-R879.
  • Guyon, N., & Nahmani, M. (2021). Role of parvalbumin interneurons in gamma oscillations and sensory processing in autism. Frontiers in Neuroscience, 15, 692872.
  • Hussman, J. P. (2001). Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism. Journal of Autism and Developmental Disorders, 31(2), 247-248.
  • Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2(5), 255-267.