parvalbumin interneurons

The GluN2A Subunit of the NMDA Receptor and Parvalbumin Interneurons: A Possible Role in Interneuron Development

N-methyl-D-aspartate receptors (NMDARs) are excitatory glutamate-gated ion channels that are expressed throughout the central nervous system. NMDARs mediate calcium entry into cells, and are involved in a host of neurological functions. The GluN2A subunit, encoded by the GRIN2A gene, is expressed by both excitatory and inhibitory neurons, with well described roles in pyramidal cells. By using Grin2a knockout mice, we show that the loss of GluN2A signaling impacts parvalbumin-positive (PV) GABAergic interneuron function in hippocampus. Grin2a knockout mice have 33% more PV cells in CA1 compared to wild type but similar cholecystokinin-positive cell density. Immunohistochemistry and electrophysiological recordings show that excess PV cells do eventually incorporate into the hippocampal network and participate in phasic inhibition. Although the morphology of Grin2a knockout PV cells is unaffected, excitability and action-potential firing properties show age-dependent alterations. Preadolescent (P20-25) PV cells have an increased input resistance, longer membrane time constant, longer action-potential half-width, a lower current threshold for depolarization-induced block of action-potential firing, and a decrease in peak action-potential firing rate. Each of these measures are corrected in adulthood, reaching wild type levels, suggesting a potential delay of electrophysiological maturation. The circuit and behavioral implications of this age-dependent PV interneuron malfunction are unknown. However, neonatal Grin2a knockout mice are more susceptible to lipopolysaccharide and febrile-induced seizures, consistent with a critical role for early GluN2A signaling in development and maintenance of excitatory-inhibitory balance. These results could provide insights into how loss-of-function GRIN2A human variants generate an epileptic phenotypes.

Synapse and Circuit Development

The symposium will start with A/Prof Jenny Gunnersen who will present “New insights into mechanisms of excitatory synapse development”. Then, Dr Tommas Ellender will deal with the “Embryonic neural progenitor pools and the generation of fine-scale neural circuits” and Dr Thomas Marissal will talk about “Parvalbumin interneurons: the missing link between the micro and macroscopic alterations related to neurodevelopmental disorders?"”.

Circuit dysfunction and sensory processing in Fragile X Syndrome

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we have adopted a symptom-to-circuit approach in theFmr1-/- mouse model of Fragile X syndrome (FXS). Using a go/no-go task and in vivo 2-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons in primary visual cortex, and a decrease in the activity of parvalbumin (PV) interneurons. Restoring visually evoked activity in PV cells in Fmr1-/- mice with a chemogenetic (DREADD) strategy was sufficient to rescue their behavioural performance. Strikingly, human subjects with FXS exhibit similar impairments in visual discrimination as Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in FXS. More recently, we find that the ability of Fmr1-/- mice to perform the visual discrimination task is also drastically impaired in the presence of visual or auditory distractors, suggesting that sensory hypersensitivity may affect perceptual learning in autism.

The interplay between oxidative stress, mitochondrial dysfunction, and alteration of parvalbumin interneurons in postmortem brain of Alzheimer’s disease and mild cognitive impairment patients

FENS Forum 2024

Parvalbumin interneurons regulate recall of associations and novelty coding by modulating attractor dynamics in ventral subiculum

COSYNE 2025

Retrosplenial Parvalbumin Interneurons Gate the Egocentric Vector Coding of Environmental Geometry

COSYNE 2025

Activity-dependent Modulation of PGC1α Regulates the Maturation of Cortical Parvalbumin Interneurons

Chemogenetic manipulations of parvalbumin interneurons as an animal model of schizophrenia: implications on behavior and electrophysiology

Investigating the mechanisms underlying the beneficial effects of exercise on cognitive impairment associated with schizophrenia - focus on parvalbumin interneurons and perineuronal nets

Involvement of nucleus accumbens parvalbumin interneurons in cocaine seeking behavior

Myelination of Parvalbumin interneurons is critical to maintain high-frequency firing and self-inhibitory neurotransmission

PNN-dependent regulation of thalamo-cortical inputs onto parvalbumin interneurons in adult mouse primary visual cortex

The role of striatal parvalbumin interneurons in decision-making

Chemogenetic modulation of parvalbumin interneurons in the medial prefrontal cortex: Relevance to cognitive schizophrenia-like symptoms in rats

FENS Forum 2024

Cortical changes in perineuronal nets and parvalbumin interneurons in chronic pain-induced mood disorders

FENS Forum 2024

Impact of hippocampal parvalbumin interneurons on memory impairment in rat models of Parkinson's disease

FENS Forum 2024

Logic of the spatial and functional organization of the cortico-striatal projections onto somatostatin and parvalbumin interneurons in the dorsal striatum of mice

FENS Forum 2024

Parvalbumin interneurons protect peritumoral tissue from glioblastoma growth

FENS Forum 2024

Optogenetic inhibition of parvalbumin interneurons in the medial striatum during a perceptual decision-making task

FENS Forum 2024

Parvalbumin interneurons are related with autistic-like behaviours and altered cortical excitability in PV-Cre/Pcdh19 cKO mice

FENS Forum 2024

A postnatal molecular switch drives the activity-dependent maturation of cortical parvalbumin interneurons

FENS Forum 2024

Social memory and prepulse inhibition in APP/PS1 mice and the effect of chemogenetic manipulation of parvalbumin interneurons in the ventral hippocampus

FENS Forum 2024

Synaptic control of microtubule organisation in parvalbumin interneurons

FENS Forum 2024