The GABA excitatory/inhibitory developmental sequence: a personal journey.
1The Autism Group and Neurochlore at INMED Inserm U901, campus scientifique de luminy, 163 route de luminy, 13273 Marseilles Cedex 09, France.
Neuroscience
|August 30, 2014
Summary
The developing brain uses excitatory GABA and high chloride levels, regulated by NKCC1 and KCC2 transporters. Disruptions can lead to developmental disorders, offering new therapeutic targets.
Area of Science:
- Developmental Neurobiology
- Neurophysiology
- Molecular Neuroscience
Background:
- Brain development involves distinct ionic currents and network patterns compared to adult brains.
- Immature brains exhibit elevated intracellular chloride (Cl(-))i levels and excitatory GABA, a conserved evolutionary sequence.
- This developmental shift is mediated by the chloride transporters NKCC1 (importer) and KCC2 (exporter).
Purpose of the Study:
- To explore the concept of 'neuroarcheology' in developmental neurobiology.
- To present a personal account of how an unexpected observation led to novel concepts.
- To discuss potential therapeutic perspectives for developmental disorders based on targeting immature neuronal currents.
Main Methods:
- Observational studies on developmental changes in ionic currents and chloride levels.
- Analysis of the role of NKCC1 and KCC2 chloride transporters in regulating GABAergic signaling.
- Examination of how genetic or environmental insults can disrupt developmental sequences.
Main Results:
- Early development features excitatory GABA and high intracellular chloride, crucial for neuritic growth and synapse formation.
- Disruptions in NKCC1 and KCC2 regulation can cause persistence of immature brain features in adults.
- Pathological conditions can exhibit a return to immature chloride levels and excitatory GABA actions.
Conclusions:
- Targeting immature neuronal currents, distinct from adult ones, offers novel therapeutic strategies for developmental disorders.
- Understanding developmental sequences is key to comprehending and treating conditions like autism.
- Scientific discovery requires time, exploration, and is often non-linear, moving from unexpected observations to significant insights.
More Related Videos
07:16Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
14.1K
05:00Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders
Published on: November 11, 2022
2.9K
Related Concept Videos
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
1.7K
γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
1.7K
01:22Activation and Inactivation of G Proteins
8.8K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
8.8K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
4.5K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.5K
01:25Rab Cascades
2.8K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.8K
01:29Excitatory and Inhibitory Effects of Neurotransmitters
11.8K
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
11.8K
01:21G-Protein Gated Ion Channels
5.4K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
5.4K