The DOI matches its Crossref record; 135 of the 135 references it cites were found in a registry or an index.
Fast-spiking, parvalbumin + GABAergic interneurons: From cellular design to microcircuit function
Abstract
Background: Neuronal networks in the brain include glutamatergic principal neurons and GABAergic interneurons (GABA, γ-aminobutyric acid). The latter may be a minority cell type, but they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, higher brain function can be damaged and seizures may result. The fast-spiking, parvalbumin-positive interneurons (PV + interneurons) are readily characterized and, consequently, have been adopted as a research model for systematic and quantitative investigations. These cells contribute to feedback and feedforward inhibition and are critically involved in the generation of network oscillations. They can convert an excitatory input signal into an inhibitory output signal within a millisecond, but it is unclear how these signaling properties are implemented at the molecular and cellular levels, nor how PV + interneurons shape complex network functions. Advances: Recent work sheds light on the subcellular signaling properties of PV + interneurons. PV + cells show a high degree of polarity. The weakly excitable dendrites allow PV + interneurons to sample activity in the surrounding network, whereas the highly excitable axons enable analog-to-digital conversion and fast propagation of the digital signal to a large number of target cells. Additionally, tight coupling of Ca 2+ channels and release sensors at GABAergic output synapses increases the efficacy and speed of the inhibitory output. Recent results also provide a better understanding of how PV + interneurons operate in neuronal networks. Not only are PV + interneurons involved in basic microcircuit functions, such as feedforward and feedback inhibition or gamma-frequency oscillations, but they also play a role in complex network operations, including expansion of dynamic activity range, pattern separation, modulation of place and grid field shapes, phase precession, and gain modulation of sensory responses. Thus, PV + interneurons are critically involved in advanced computations in microcircuits and neuronal networks. Outlook: Parvalbumin-expressing interneurons may also play a key role in numerous brain diseases. These include epilepsy, but also complex psychiatric diseases such as schizophrenia. Thus, PV + interneurons may become important therapeutic targets in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will have a chance to successfully use PV + interneurons for therapeutic purposes.
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“Fast-spiking (FS) CA1 interneurons (classically referred to as “theta cells”53) have been mechanistically linked to the emergence of the LFP theta rhythm and the entrainment of pyramidal neurons in the hippocampus42,54–56.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [55]
In the citing paper
“Fast-spiking interneurons expressing the calcium binding protein parvalbumin (PV+) are the main modulators of critical period plasticity (Figure 4).”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [38]
In the citing paper
“These cells provide very strong inhibition to pyramidal cells 38 , and so their maturation rapidly restricts the influence of sensory experience in pyramidal cells and leads to the closure of critical period plasticity.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [38]
In the citing paper
“Although PNNs are stable structures and known to lock synapses in place upon closure of the developmental window of plasticity17,38,39, several CNS pathologies40, including glioma and epilepsy, present with upregulated ECM and PNN remodeling enzymes including MMPs.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [38]
In the citing paper
“PV-INs have roles in both feedforward and feedback inhibition, regulation of sensory responses, and in learning and plasticity [66].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [66]
In the citing paper
“For this reason, the characteristic phenotype of PV-INs is fast-spiking action potentials at high energetic costs [66].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [66]
In the citing paper
“They help to create and maintain gamma oscillations, which are high-frequency waves between 20 and 100 Hz [66,75].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [66]
In the citing paper
“Certain morphological features might be more tightly linked to connectivity (for example, CHC axon arborizations39), and certain intrinsic and synaptic features might be better linked to I/O properties (for instance, fast-spiking basket cells show fast in–fast out signal dynamics66).”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [66]
In the citing paper
“Instead, different components, such as synaptic inputs and integration, spike initiation and propagation, and synaptic release, are measured separately only in a few abundant and accessible cell populations (for example, parvalbumin-expressing fast-spiking basket cells66).”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [66]
In the citing paper
“The last two decades have strengthened early observations suggesting that the complement of both voltage- and ligand-gated channels expressed on hippocampal inhibitory interneurons differs markedly from those expressed on their glutamatergic principal cell counterparts (502, 641, 770).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“In consideration of these data, Hu et al. (502) reasoned that Kv1 channels may impose a fast coincidence detection mechanism in PV-containing interneurons, allowing fast EPSPs to beat Kv1 activation leading to a rapid action potential initiation with little delay.”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“Kv3 expression is highest in dendrites of cells that typically possess low dendritic Na+ channel densities (502, 504).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“In addition, action potential propagation and transmitter release components cannot support the rapid throughput typically observed in mature cells.”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“Consequently, during the first two to three postnatal weeks of life, action potential duration, propagation time, and duration of the transmitter release period decrease by ~50% as a result of the concurrent functional maturation of cell morphology, voltage-gated Na+ and K+ currents, as well as refinement of the presynaptic release machinery (277, 502).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“At early postnatal stages, action potential firing is slow and unable to sustain periods of high-frequency activity.”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“The molecular identities of Na+ channels in interneurons suggest that at least in PVBCs the vast majority of Na+ channels are formed by Nav1.1 and Nav1.6 subunits with a lesser contribution from Nav1.2, Nav1.4, and Nav1.7 (502, 695, 857, 852).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“The Ca2+ binding properties of syt2 likely serve to minimize the time required between Ca2+ entry and the liberation of neurotransmitter (502).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“As a consequence of these molecular specializations, the small number of Ca2+ channels at each release site coupled to syt2-mediated neurotransmitter release favors fast temporally precise “synchronous” phasic transmitter release, thus making them rapid signaling devices capable of providing precisely timed inhibition onto their postsynaptic cells (64, 502) (FIGURE 13).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
In the citing paper
“This receptor arrangement is critical for circuit recruitment of PV-containing interneurons to enforce temporal control over principal cells for efficient generation of large scale oscillatory activity (for review, see Refs. 67, 502).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [502]
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Metadata
- Authors
- Hu, H., Gan, J., & Jonas, P.
- Affiliations
- Institute of Science and Technology Austria (AT)
- IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria.
- Venue
- Science
- Published
- 2014-08
- Volume
- 345
- Issue
- 6196
- Pages
- 1255263-1255263
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2084072056
- Cited by
- 1,197
- References
- 135
- Citations by year
- 2026: 95 · 2025: 129 · 2024: 115 · 2023: 94 · 2022: 103 · 2021: 143 · 2020: 141 · 2019: 102 · 2018: 92 · 2017: 59 · 2016: 66 · 2015: 52 · 2014: 5
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- parvalbumin interneurons, fast-spiking neurons, GABAergic interneurons, neuronal polarity, dendritic excitability, calcium channels, synaptic inhibition, feedforward inhibition, product inhibition, gamma oscillations, pattern separation, phase precession, grid cells, place cells, gain modulation, epilepsy, schizophrenia, therapeutic target
- MeSH terms
- Action Potentials, Animals, Mental Disorders, Brain Diseases, Interneurons, Nerve Net, Synaptic Transmission, Parvalbumins, Mice, Synaptic Potentials, GABAergic Neurons
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