Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo.

In addition to numerous GABA-ergic efferent neurons, the striatum contains a subpopulation of fast-firing GABA-ergic interneurons characterized by the presence of immunoreactivity for the calcium-binding protein, parvalbumin. Double-label in situ hybridization with digoxigenin- and radiolabelled cRNA probes was performed on striatal sections of adult rats to identify mRNAs expressed by striatal GABA-ergic interneurons. In the dorsolateral striatum, only parvalbumin mRNA-positive neurons expressed the mRNA encoding the potassium channel Kv3.1, a member of the Shaw family of potassium channels with rapid activation and inactivation kinetics, usually found in fast-firing neurons such as the basket cells of the hippocampus. Colocalization of the parvalbumin and Kv3.1 proteins was confirmed by double-label immunohistochemistry. Parvalbumin mRNA-positive neurons expressed very high levels of the mRNA encoding glutamic acid decarboxylase (Mr 67,000: GAD67) in the dorsolateral striatum. A smaller proportion of double-labelled neurons was found in the ventrolateral striatum. A small number of densely labelled neurons for GAD67 mRNA also expressed the mRNA encoding the dopamine D2 receptor, but none expressed detectable levels of the dopamine D1 receptor mRNA. This indicates major differences in the expression of dopamine receptor mRNA in a majority of GABA-ergic interneurons vs. GABA-ergic efferent neurons of the striatum. The results suggest that distinct molecular characteristics are associated with the distinct electrophysiological properties of striatal GABA-ergic neurons.

Dopamine is an important neurotransmitter that exhibits numerous functions in the healthy, injured, and diseased brain. Fast scan cyclic voltammetry paired with electrical stimulation of dopamine axons is a popular and powerful method for investigating the dynamics of dopamine in the extracellular space. Evidence now suggests that the heterogeneity of electrically evoked dopamine responses reflects the inherent kinetic diversity of dopamine systems, which might contribute to their diversity of physiological function. Dopamine measurements by fast scan cyclic voltammetry are affected by the adsorption of dopamine to carbon fiber electrodes. The temporal distortion caused by dopamine adsorption is correctable by a straightforward mathematical procedure. The corrected responses exhibit excellent agreement with a dopamine kinetic model cast to provide a generic description of restricted diffusion, short-term plasticity of dopamine release, and first-order dopamine clearance. The new DA kinetic model brings to light the rich kinetic information content of electrically evoked dopamine responses recorded via fast scan cyclic voltammetry in the rat dorsal striatum.

Intracerebral microdialysis has proven useful for chemical monitoring in patients following traumatic brain injury. Recent studies in animals, however, have documented that insertion of microdialysis probes into brain tissues initiates a foreign-body response. Within a few days after probe insertion, the foreign body response impedes the use of microdialysis to monitor the K + and glucose transients associated with spreading depolarization, a potential mechanism for secondary brain injury. Herein, we show that perfusing microdialysis probes with dexamethasone, a potent anti-inflammatory glucocorticoid, suppresses the foreign body response and facilitates the monitoring of spontaneous spreading depolarizations for at least 10 days following controlled cortical injury in the rat. In addition to spreading depolarizations, results of this study suggest that a progressive, apparently permanent, decline in pericontusional interstitial glucose may be an additional sequela of brain injury. This study establishes extended dexamethasone-enhanced microdialysis in the injured rodent cortex as a new paradigm for investigating trauma-induced metabolic crisis.

The brain is a complex network that accounts for only 5% of human mass but consumes 20% of our energy. Uncovering the mysteries of the brain’s functions in motion, memory, learning, behavior, and mental health remains a hot but challenging topic. Neurochemicals in the brain, such as neurotransmitters, neuromodulators, gliotransmitters, hormones, and metabolism substrates and products, play vital roles in mediating and modulating normal brain function, and their abnormal release or imbalanced concentrations can cause various diseases, such as epilepsy, Alzheimer’s disease, and Parkinson’s disease. A wide range of techniques have been used to probe the concentrations of neurochemicals under normal, stimulated, diseased, and drug-induced conditions in order to understand the neurochemistry of drug mechanisms and develop diagnostic tools or therapies. Recent advancements in detection methods, device fabrication, and new materials have resulted in the development of neurochemical sensors with improved performance. However, direct in vivo measurements require a robust sensor that is highly sensitive and selective with minimal fouling and reduced inflammatory foreign body responses. Here, we review recent advances in neurochemical sensor development for in vivo studies, with a focus on electrochemical and optical probes. Other alternative methods are also compared. We discuss in detail the in vivo challenges for these methods and provide an outlook for future directions.

Radioactively labeled RNA probes in conjunction with in situ hybridization histochemistry have become a useful method for studying gene expression in the central nervous system. We used digoxigenin-labeled uridine triphosphate to synthesize cRNA probes for localization of nerve growth factor receptor (NGFR) mRNA in the rat basal forebrain. Detection of cells containing &goxigethn-labeled NGFR mRNA was accomplished using a digoxigenin antibody conjugated with alkaline phosphatase. NGFR mRNA-positive cells were distributed in three major cell groups in the basal

Dopamine (DA) plays a central role in the modulation of various physiological brain functions, including learning, motivation, reward, and movement control. The DA dynamic occurs over multiple timescales, including fast phasic release, as a result of neuronal firing and slow tonic release, which regulates the phasic firing. Real-time measurements of tonic and phasic DA concentrations in the living brain can shed light on the mechanism of DA dynamics underlying behavioral and psychiatric disorders and on the action of pharmacological treatments targeting DA. Current state-of-the-art in vivo DA detection technologies are limited in either spatial or temporal resolution, channel count, longitudinal stability, and ability to measure both phasic and tonic dynamics. We present here an implantable glassy carbon (GC) multielectrode array on a SU-8 flexible substrate for integrated multichannel phasic and tonic measurements of DA concentrations. The GC MEA demonstrated in vivo multichannel fast-scan cyclic voltammetry (FSCV) detection of electrically stimulated phasic DA release simultaneously at different locations of the mouse dorsal striatum. Tonic DA measurement was enabled by coating GC electrodes with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) and using optimized square-wave voltammetry (SWV). Implanted PEDOT/CNT-coated MEAs achieved stable detection of tonic DA concentrations for up to 3 weeks in the mouse dorsal striatum. This is the first demonstration of implantable flexible MEA capable of multisite electrochemical sensing of both tonic and phasic DA dynamics in vivo with chronic stability.

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