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GABAergic Neuron Markers

Kai Boon Tan, PhD | 5th June 2025

GABAergic neurons are inhibitory neurons that produce and release the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).1 These neurons are critical in balancing neural circuits by inhibiting excitatory signals, thereby orchestrating neural activity.2,3 Dysregulation of GABAergic function is linked to epilepsy,4,5 anxiety disorders,6,7 schizophrenia8,9 and autism spectrum disorders,10–12 making GABAergic neurons a major focus of neuroscience research.

Studying GABAergic neurons often requires specific molecular markers, such as glutamate decarboxylase (GAD65/67), vesicular GABA transporter (VGAT), GABA transporter 1 (GAT-1) and GABA itself. This guide highlights the most widely used pan-GABAergic neuron markers for characterizing and analyzing GABAergic neurons across applications such as IHC and ICC/IF. For markers of GABAergic cortical interneurons such as parvalbumin and somatostatin, see our Interneuron Markers page. Below are examples of how GABAergic neuron markers can be used in neuroscience research:

  • Visualize GABAergic neuron populations in a brain region assayed using transcriptomic technologies.
  • Identify in vivo GABAergic neural circuits following electrophysiology or in vivo calcium imaging experiments in conjunction with genetic fate-mapping.
  • Characterize the GABAergic neurons differentiated in in vitro 2D or 3D organoid culture systems.
  • Study the shift of GABAergic neuronal fate in disease models or upon the perturbation of transcriptional regulation.

Explore allSee GABAergic Neuron Marker Antibodies

Table of Contents

Core GABAergic Markers

Molecular Marker Protein Type Description
GABA Neurotransmitter The primary inhibitory neurotransmitter in the nervous system.
GAD65, GAD67 Enzymes Enzymes essential for GABA biosynthesis.
VGAT Transporter Transporter that transports GABA from the cytoplasm into synaptic vesicles.
GAT1 Transporter Transporter responsible to the reuptake of GABA from the synaptic cleft back into presynaptic neurons.

Table 1: Summary of common molecular markers used to characterize GABAergic neurons.

GABAergic Neurotransmission

GABAergic neurons play a crucial role in brain activity by reducing excitatory neuron activity, thus maintaining the balance between excitation and inhibition essential for proper brain function.13 They achieve this by releasing GABA into the synaptic cleft, where it binds to the specific GABA-A and GABA-B receptors on neighboring neurons.14–16 Activation of these receptors causes chloride ions to influx and potassium ions to efflux, leading to hyperpolarization of the postsynaptic neuron and rendering it less likely to fire an action potential.

GABAergic neurons are widely distributed across the nervous system,1 including the cerebral cortex, amygdala, hippocampus, hypothalamus, spinal cord and peripheral nervous system, such as sensory ganglia17 and vagus nerve.18 They are particularly important for controlling the flow of information, synchronizing neural networks, and preventing excessive neuronal firing.1,13 In the cerebral cortex, GABAergic interneurons modulate the activity of excitatory glutamatergic neurons, contributing to the fine-tuning of behaviors, motor control, mood and sleep.13,19

GABA

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. Its main function is to reduce neuronal excitability, thereby maintaining the balance between neural excitation and inhibition. When GABA binds to GABA receptors, it typically results in the influx of chloride ions into the neuron (via GABA-A receptors) or the efflux of potassium ions (via GABA-B receptors), ultimately making the neuron less likely to fire an action potential.15,16,20 GABA's inhibitory action is terminated by reuptake into neurons and glial cells via GAT1, where it is then metabolized.21

Although the presence of GABA definitively marks a neuron as GABAergic, direct immunostaining for GABA is technically challenging. GABA is a small molecule that lacks firm anchorage to cellular structures, meaning it can be washed out or lost during fixation. Furthermore, producing highly specific antibodies against small, non-immunogenic molecules (called haptens) is inherently more difficult than for large proteins. For these reasons, marking GABAergic neurons tends to rely on the marker proteins described below.

GABA IHC in neuronal culture

Figure 1: IHC directly against GABA. IHC of neuronal culture stained with GABA in green, surface GABA-A receptors (β2/3 subunit) in red, and DAPI in blue. Right image an enlarged image of a neuronal process. Edited and reproduced from 22.

GAD65 and GAD67

The glutamate decarboxylases (GADs) are key enzymes responsible for converting glutamate into GABA in GABAergic neurons.23,24 In mammals, GAD exists in two main isoforms, GAD65 and GAD67, named after their molecular weights of 65 kDa and 67 kDa, respectively. GAD65, encoded by the GAD2 gene, is primarily involved in synthesising GABA at synaptic terminals and is dynamically regulated during neurotransmission.25 GAD67, encoded by GAD1, is constitutively active and more widely distributed in the cytoplasm, and is thought to synthesize GABA for other cellular processes such as development and metabolic functions.26

IHC - Anti-GAD65 Antibody (A12729)

Figure 2: IHC of rat brain tissue stained with Anti-GAD65 Antibody (A12729) in red. Nuclei were stained by DAPI in blue.

IHC - Anti-GAD67 Antibody (A14262)

Figure 3: IHC of rat eye cells stained with Anti-GAD67 Antibody (A14262) in red. Nuclei were stained by DAPI in blue.

VGAT

Vesicular GABA transporter (VGAT or SLC32A1) is a protein usually found in the nerve endings of GABAergic and glycinergic neurons. Its primary function is to package and transport GABA and glycine from the neuron cytoplasm into synaptic vesicles.27,28 VGAT is also known as the vesicular inhibitory amino acid transporter (VIAAT) and is the only member of the SLC32 transporter family. VGAT operates as an antiporter to drive the accumulation of GABA and glycine within vesicles via the proton electrochemical gradient generated by vacuolar H+-ATPase.29 Research has also shown that VGAT can transport β-alanine within GABAergic neurons,30 suggesting a broader substrate specificity than previously thought.31

GAT1

Gamma-aminobutyric acid transporter 1 (GAT1, encoded by the SLC6A1 gene) is a member of the solute carrier 6 (SLC6) family. It is responsible for the reuptake of GABA from the synaptic cleft back into the presynaptic neurons or astrocytes.21 This reuptake process terminates GABAergic signaling, thereby modulating the duration and intensity of inhibitory neurotransmission.32 GAT1 operates through the electrochemical gradients of sodium and chloride ions, with a typical stoichiometry of 2 Na+:1 Cl-:1 GABA per transport cycle.33 During the transport cycle, GAT1 undergoes conformational changes and enables the sequential binding and release of ions and GABA, ensuring efficient removal of GABA from the synaptic cleft.33,34

IHC - Anti-SLC6A1 Antibody (A96733)

Figure 4: IHC of human brain tissue stained with Anti-SLC6A1 Antibody (A96733).

GABAergic Neuron Marker Antibodies

GABA ELISA Kits
GAD65 Antibodies
GAD1 Antibodies
GAT1 Antibodies
VGAT Antibodies

References

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  3. Perea, G. et al. Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks. eLife 5, e20362 (2016).
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  21. Kanner, B. I. & Dayan-Alon, O. GABA transport goes structural. Trends Pharmacol. Sci. 44, 4–6 (2023).
  22. Wang, P. et al. Neuronal gamma-aminobutyric acid (GABA) type A receptors undergo cognate ligand chaperoning in the endoplasmic reticulum by endogenous GABA. Front. Cell. Neurosci. 9, (2015).
  23. Walls, A. B. et al. GAD65 is essential for synthesis of GABA destined for tonic inhibition regulating epileptiform activity. J. Neurochem. 115, 1398–1408 (2010).
  24. Buddhala, C., Hsu, C.-C. & Wu, J.-Y. A novel mechanism for GABA synthesis and packaging into synaptic vesicles. Glutamate Tripart. Synap. Funct. Metab. Relat. Norm Pathol. 55, 9–12 (2009).
  25. Tian, N. et al. The role of the synthetic enzyme GAD65 in the control of neuronal γ-aminobutyric acid release. Proc. Natl. Acad. Sci. 96, 12911–12916 (1999).
  26. Tavazzani, E. et al. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells. Front. Cell. Neurosci. 8, (2014).
  27. Chaudhry, F. A. et al. The Vesicular GABA Transporter, VGAT, Localizes to Synaptic Vesicles in Sets of Glycinergic as Well as GABAergic Neurons. J. Neurosci. 18, 9733 (1998).
  28. Wojcik, S. M. et al. A Shared Vesicular Carrier Allows Synaptic Corelease of GABA and Glycine. Neuron 50, 575–587 (2006).
  29. McIntire, S. L., Reimer, R. J., Schuske, K., Edwards, R. H. & Jorgensen, E. M. Identification and characterization of the vesicular GABA transporter. Nature 389, 870–876 (1997).
  30. Juge, N., Omote, H. & Moriyama, Y. Vesicular GABA transporter (VGAT) transports β-alanine. J. Neurochem. 127, 482–486 (2013).
  31. le Feber, J., Dummer, A., Hassink, G. C., van Putten, M. J. A. M. & Hofmeijer, J. Evolution of Excitation–Inhibition Ratio in Cortical Cultures Exposed to Hypoxia. Front. Cell. Neurosci. 12, (2018).
  32. Nayak, S. R. et al. Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism. Nat. Struct. Mol. Biol. 30, 1023–1032 (2023).
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  34. Zafar, S. & Jabeen, I. Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective. Front. Chem. 6, (2018).
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