Modulation Of Neuronal Activity Research Articles

Vasoactive intestinal peptide-expressing interneurons modulate the effect of behavioral state on cortical activity.

Animals live in a complex and changing environment with various degrees of behavioral demands. Behavioral states affect the activity of cortical neurons and the dynamics of neuronal populations, however not much is known about the cortical circuitry behind the modulation of neuronal activity across behavioral states. Here we show that a class of GABAergic inhibitory interneurons that express vasoactive intestinal peptide-expressing interneurons (VIP), namely VIP interneurons, play a key role in the circuits involved in the modulation of cortical activity by behavioral state, as reflected in the mice facial motion. We show that inhibition of VIP interneurons reduces the correlated activity between the behavioral state of the animal and the spiking of individual neurons. We also show that VIP inhibition during the quiet state decreases the synchronous spiking of the neurons but increases delta power and phase locking of spiking to the delta-band activity. Taken together our data show that VIP interneurons modulate the behavioral state-dependency of cortical activity across different time scales.

Modulation of neuronal activity in cortical organoids with bioelectronic delivery of ions and neurotransmitters

Precise modulation of brain activity is fundamental for the proper establishment and maturation of the cerebral cortex. To this end, cortical organoids are promising tools to study circuit formation and the underpinnings of neurodevelopmental disease. However, the ability to manipulate neuronal activity with high temporal resolution in brain organoids remains limited. To overcome this challenge, we introduce a bioelectronic approach to control cortical organoid activity with the selective delivery of ions and neurotransmitters. Using this approach, we sequentially increased and decreased neuronal activity in brain organoids with the bioelectronic delivery of potassium ions (K+) and γ-aminobutyric acid (GABA), respectively, while simultaneously monitoring network activity. This works highlights bioelectronic ion pumps as tools for high-resolution temporal control of brain organoid activity toward precise pharmacological studies that can improve our understanding of neuronal function.

Central neuropathic pain.

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron-glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

Chemogenetics for cell-type-specific modulation of signalling and neuronal activity

Chemogenetics for cell-type-specific modulation of signalling and neuronal activity

Chemogenetics for cell-type-specific modulation of signalling and neuronal activity

Chemogenetics for cell-type-specific modulation of signalling and neuronal activity

Mechanistic modeling of tau biomarkers for amyloid load. A Quantitative Systems Pharmacology study of amyloid‐tau interaction.

AbstractBackgroundRecent clinical trials with amyloid antibodies have suggested a beneficial effect on cognitive scales after clearing most of the amyloid load. Interestingly, substantial reduction in plasma or CSF tau biomarkers were documented providing interesting insights into the amyloid‐tau interactions in the human AD patient.MethodWe developed a Quantitative Systems Pharmacology (QSP) platform for late MCI‐prodromal AD subjects that combined an earlier published Physiology‐Based Pharmacokinetic (PBPK)‐ QSP model of amyloid aggregation with a novel QSP model describing the impact of amyloid monomers on glutamatergic and nicotinic neurotransmission and neuronal firing, the neuronal activity‐dependent tau release, subsequent tau uptake in the afferent neuron and dynamics of tau biomarkers in CSF and plasma.ResultThe combined model quantitatively reproduced (1) the cortical hyperactivity and higher tau biomarker levels associated with increasing amyloid deposition in observational studies, (2) the differential decrease in CSF and plasma tau biomarkers in clinical trials with various amyloid antibodies. Dynamics of monomeric brain Ab40 and Ab42 and their effect on neuronal firing, rather than reduction in SUVR can better explain the clinically observed changes in CSF or plasma tau between aducanumab, lecanemab, donanemab and gantenerumab. The range of commonly used comedications and common dopaminergic and serotonergic genotype variants affecting neuronal activity can partially explain the variability of tau biomarkers response as downstream effects of amyloid removal.ConclusionThis study suggests a direct link between amyloid dynamics and plasma / CSF tau levels through modulation of neuronal activity. The calibrated QSP model sets the stage for modeling long‐term effects of amyloid therapy on tau pathology progression and identification of optimal trial design for combination therapies.

SAT592 Sexually Dimorphic Modulation Of Arcuate Kisspeptin Neurons Activity In Response To NPY

Abstract Disclosure: N.D. Mansano: None. R. Frazao: None. Kisspeptin neurons are part of an intricate brain circuit that receives neuronal inputs related tonutritional status from at least three neuronal populations, including NPY/AgRP and POMC neurons of the arcuate nucleus of the hypothalamus (ARH) and cells in the ventral premammillary nucleus. Its well-known action on the HPG axis, hypothalamic kisspeptin neurons also modulate the activity of specific neurons of the paraventricular and the dorsomedial nuclei of the hypothalamus, regions involved in the regulation of appetite and energy expenditure. However, it is not completely elucidated if NPY can influence the HPG axis through the modulation of kisspeptin neuron activity. To determine the NPY effect in the hypothalamic kisspeptin neurons we performed whole-cell patch-clamp recordings. The hypothalamic slices were obtained from the adult Kiss1/hrGFP female (diestrus-stage) or male mice. Kisspeptin cells located in the arcuate nucleus of the hypothalamus (ARHkisspeptin) and at the anteroventral periventricular and rostral periventricular nuclei (AVPV/PeNkisspeptin) were recorded. On female mice, ARHkisspeptin neurons exhibited a rest membrane potential (RMP) average of -52.5±2.5 mV (-40 to -62 mV) and 1.3±0.2 GΩ input resistance (IR). NPY induced the hyperpolarization of 45% of the ARHkisspeptin neurons (n= 9 of 20 cells, out of 9 mice). ARHkisspeptin neuron’s RMP hyperpolarization was followed by a significant decrease in IR and frequency of action potentials (fAPS). In the AVPV/PeNkisspeptin neurons showed RMP average of -69.6±1.9 mV (-51 to - 88 mV) and IR of 0.8±0.09 GΩ (n=18 cells out of 9 mice). No significant NPY-induced effect was noted when recordings were performed on AVPV/PeNkisspeptin cells from female mice. To elucidate if the ARHkisspeptin neuron’s hyperpolarization depends on action potentials (APs) mediated by synaptic transmission we further evaluated NPY effects in the presence of TTX and amino acid receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10μM), DL-2-amino-5-phosphonopentanoic acid (AP5, 50μM), and picrotoxin (50μM). NPY induced no effect on ARHkisspeptin neuron’s RMP, and IR in the presence of TTX and amino acid receptor antagonists. Suggesting that NPY-induced hyperpolarization of ARHkisspeptin neurons is an indirect effect. To further verify whether sex must be considered as a biological variable to study the NPY effect, we recorded ARHkisspeptin cells from male mice. ARHkisspeptin neurons recorded from male mice exhibited RPM average of -55.6±1.5 (-45 to -66 mV) and IR of 1.5±0.15 GΩ (n= 13 cells out of 10 mice). Interestingly, NPY induced no effect on RMP, IR, or fAPs in male animals. In conclusion, our results suggest that NPY-induced hyperpolarization of ARHkisspeptin cells depends on AP’s mediate synaptic transmission, as a sex-specific effect. Presentation: Saturday, June 17, 2023

Neuronal Activity Changes the Number of Neurons That Are Synaptically Connected to OPCs.

The timing and specificity of oligodendrocyte myelination during development, as well as remyelination after injury or immune attack, remain poorly understood. Recent work has shown that oligodendrocyte progenitors receive synapses from neurons, providing a potential mechanism for neuronal-glial communication. In this study, we investigated the importance of these neuroglial connections in myelination during development and during neuronal plasticity in the mouse hippocampus. We used chemogenetic tools and viral monosynaptic circuit tracing to analyze these connections and to examine oligodendrocyte progenitor cells (OPCs) proliferation, myelination, synapse formation, and neuronal-glial connectivity in vivo after increasing or decreasing neuronal activity levels. We found that increasing neuronal activity led to greater OPC activation and proliferation. Modulation of neuronal activity also altered the organization of neuronal-glial connections: while it did not impact the total number of RabV-labeled neuronal inputs, or the number of RabV-labeled inhibitory neuronal (IN) inputs, it did alter the number of RabV-labeled excitatory neuron to OPC connections. Overall, our findings support the idea that neuronal activity plays a crucial role in regulating OPC proliferation and activation as well as the types of neuronal inputs to OPCs, indicating that neuronal activity is important for OPC circuit composition and function.

Neuroprotection by Polyherbal Medicine Divya-Medha-Vati Against Scopolamine-Induced Cognitive Impairment Through Modulation of Oxidative Stress, Acetylcholine Activity, and Cell Signaling.

Alzheimer disease is associated with cognitive impairments and neuronal damages. In this study, Scopolamine, a model drug used for the generation of Alzheimer-like symptoms induced cognitive dysfunction in C57BL/6 mice. It also elevated acetylcholine esterase (AcHE) activity, and reduced antioxidant (superoxide dismutase and catalase) activity in cortex tissue. Scop reduced neuronal density and increased pyknotic neurons in hippocampus tissue. In mouse neuroblastoma (Neuro2a) cells, Scop triggered a dose-dependent loss of cell viability and neurite outgrowth reduction. Scop-treated Neuro2a cells showed oxidative stress and reduction in mRNA expression for brain-derived neurotrophic factor (BDNF), nerve growth factor-1 (NGF-1), and Synapsin-1 (SYN-1) genes. Mice treated with Divya-Medha-Vati (DMV), an Ayurvedic polyherbal medicine showed protection against Scop-induced cognitive impairment (Morris Water Maze Escape Latency, and Elevated Plus Maze Transfer Latency). DMV protected against Scop-induced AcHE activity, and loss of antioxidant activities in the mice brain cortex while sustaining neuronal density in the hippocampus region. In the Neuro2a cells, DMV reduced Scop-induced loss of cell viability and neurite outgrowth loss. DMV protected the cells against induction of oxidative stress and promoted mRNA expression of BDNF, NGF-1, and SYN-1 genes. Phytochemical profiling of DMV showed the presence of Withanolide A, Withanolide B, Bacopaside II, Jujubogenin, Apigenin, Gallic acid, Caffeic acid, and Quercetin that are associated with antioxidant and neurostimulatory activities. In conclusion, the study showed that Divya-Medha-Vati was capable of promoting neuronal health and inhibiting Alzheimer-like cognitive dysfunction through enhanced antioxidant activities and modulation of neuronal activities.

Poster Session: Time resolved modulation of neuronal activity associated with attention to low-level visual features.

During eye growth, scleral development critically determine eye size and thus the refractive status of the eye. Scleral remodeling in myopia includes scleral thinning, loss of scleral tissue, and weakening of the mechanical properties. Therefore, an intervention aiming at stiffening scleral tissues (crosslinking, SCXL) may provide a way to prevent or treat myopia. The development of SCXL requires tools to evaluate the effects of crosslinking on the mechanical properties of tissues, particularly in sclera where the mechanical properties are more spatially heterogeneous than in the cornea, anisotropic, and varying locally from the anterior to posterior regions. Here, we apply the high-frequency OCE technique to measure the heterogeneous mechanical properties of posterior scleral tissues and, evaluate the changes in shear moduli after SCXL. As a model system, we use ex vivo in porcine eyes and riboflavin-assisted UV crosslinking. From measured elastic wave speeds (6-16kHz), the average out-of-plane shear modulus was 0.71±0.12MPa (n=20) for normal scleras. After treatment, the shear modulus increased to 1.50±0.39MPa. This 2-fold change was consistent with the increase of static Young's modulus from 5.5±.1 to 9.3±1.9MPa after crosslinking, using conventional uniaxial extensometry. OCE revealed regional stiffness differences across the temporal, nasal, and deeper posterior sclera, demonstrating its potential as a noninvasive tool to test the effect of scleral crosslinking.

A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain

Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel vector of which capsid was composed of capsid proteins derived from both of the AAV serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for AAV1 vector) and neuron specificity (for AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.

Connectivity of the Brain in the Light of Chemogenetic Modulation of Neuronal Activity.

Connectivity is the coordinated activity of the neuronal networks responsible for brain functions; it is detected based on functional magnetic resonance imaging signals that depend on the oxygen level in the blood (blood oxygen level-dependent (BOLD) signals) supplying the brain. The BOLD signal is only indirectly related to the underlying neuronal activity; therefore, it remains an open question whether connectivity and changes in it are only manifestations of normal and pathological states of the brain or they are, to some extent, the causes of these states. The creation of chemogenetic receptors activated by synthetic drugs (designer receptors exclusively activated by designer drugs, DREADDs), which, depending on the receptor type, either facilitate or, on the contrary, inhibit the neuronal response to received physiological stimuli, makes it possible to assess brain connectivity in the light of controlled neuronal activity. Evidence suggests that connectivity is based on neuronal activity and is a manifestation of connections between brain regions that integrate sensory, cognitive, and motor functions. Chemogenetic modulation of the activity of various groups and types of neurons changes the connectivity of the brain and its complex functions. Chemogenetics can be useful in reconfiguring the pathological mechanisms of nervous and mental diseases. The initiated integration, based on the whole-brain connectome from molecular-cellular, neuronal, and synaptic processes to higher nervous activity and behavior, has the potential to significantly increase the fundamental and applied value of this branch of neuroscience.

Neuronal activity and NIBS in developmental myelination and remyelination - Current state of knowledge.

Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials. Myelination and myelin repair rely partially on oligodendrogenesis, which comprises oligodendrocyte precursor cell (OPC) migration, maturation, and differentiation into oligodendrocytes (OL). In multiple sclerosis (MS), demyelination occurs due to an inflammatory cascade with auto-reactive T-cells. When oligodendrogenesis fails, remyelination becomes aberrant and conduction impairments are no longer restored. Although current disease modifying therapies have achieved results in modulating the faulty immune response, disease progression continues because of chronic inflammation, neurodegeneration, and failure of remyelination. Therapies have been tried to promote remyelination. Modulation of neuronal activity seems to be a very promising strategy in preclinical studies. Additionally, studies in people with MS (pwMS) have shown symptom improvement following non-invasive brain stimulation. (NIBS) techniques. The aforementioned mechanisms are yet unknown and probably involve both the activation of neurons and glial cells. Noting neuronal activity contributes to myelin plasticity and that NIBS modulates neuronal activity; we argue that NIBS is a promising research horizon for demyelinating diseases. We review the hypothesized pathways through which NIBS may affect both neuronal activity in the CNS and how the resulting activity can affect oligodendrogenesis and myelination.

Morphological characteristics of astrocytes of the fastigial nucleus

Astrocytes are a diverse and morphologically complex class of glial cells restricted to the central nervous system which have been implicated in the modulation of neuronal activity. The cerebellum is involved in planning movements and motor learning. Within the cerebellum three deep cerebellar nuclei (dentate, interposed and fastigial) provide the sole neuronal output. The fastigial nucleus participates in saccadic and vestibular function, and recent evidence disclosed neuronal projections to cognitive, affective, and motor areas. However, thus far there are no reliable descriptions of the distribution and morphological classifications of astrocytes in this nucleus. This work aims to describe the characteristics of astrocytes of the fastigial nucleus based on the expression of GFP in a transgenic mouse model.

Interactions between the Astrocytic Volume-Regulated Anion Channel and Aquaporin 4 in Hyposmotic Regulation of Vasopressin Neuronal Activity in the Supraoptic Nucleus.

We assessed interactions between the astrocytic volume-regulated anion channel (VRAC) and aquaporin 4 (AQP4) in the supraoptic nucleus (SON). Acute SON slices and cultures of hypothalamic astrocytes prepared from rats received hyposmotic challenge (HOC) with/without VRAC or AQP4 blockers. In acute slices, HOC caused an early decrease with a late rebound in the neuronal firing rate of vasopressin neurons, which required activity of astrocytic AQP4 and VRAC. HOC also caused a persistent decrease in the excitatory postsynaptic current frequency, supported by VRAC and AQP4 activity in early HOC; late HOC required only VRAC activity. These events were associated with the dynamics of glial fibrillary acidic protein (GFAP) filaments, the late retraction of which was mediated by VRAC activity; this activity also mediated an HOC-evoked early increase in AQP4 expression and late subside in GFAP-AQP4 colocalization. AQP4 activity supported an early HOC-evoked increase in VRAC levels and its colocalization with GFAP. In cultured astrocytes, late HOC augmented VRAC currents, the activation of which depended on AQP4 pre-HOC/HOC activity. HOC caused an early increase in VRAC expression followed by a late rebound, requiring AQP4 and VRAC, or only AQP4 activity, respectively. Astrocytic swelling in early HOC depended on AQP4 activity, and so did the early extension of GFAP filaments. VRAC and AQP4 activity supported late regulatory volume decrease, the retraction of GFAP filaments, and subside in GFAP-VRAC colocalization. Taken together, astrocytic morphological plasticity relies on the coordinated activities of VRAC and AQP4, which are mutually regulated in the astrocytic mediation of HOC-evoked modulation of vasopressin neuronal activity.

The Role of Genes and Proteins in Neurons Functioning

Purpose: The aim of the study is to examine the role of genes and proteins in neurons functioning.
 Methodology: This study adopted a desktop methodology. This study used secondary data from which include review of existing literature from already published studies and reports that was easily accessed through online journals and libraries.
 Findings: The study revealed that genes and proteins play pivotal roles in the functioning of neurons, contributing to the complex processes involved in neural development, communication, and plasticity. Genes provide the instructions for the production of proteins, which act as the building blocks and functional molecules within cells. The interplay between genes and proteins is essential for various neuronal processes, including synaptic transmission, neural circuit formation, and the modulation of neuronal activity.
 Unique Contribution to Theory, Practice and Policy: The study was anchored on the theory of synaptic plasticity which was proposed by Donald Hebb and the theory of neurotransmission which was pioneered by Otto Loewi. The study recommends that policies should be developed to promote genetic screening and testing for neurological disorders, allowing for early interventions and improved outcomes.

Self-assembled ultraflexible probes for long-term neural recordings and neuromodulation.

Ultraflexible microelectrode arrays (MEAs) that can stably record from a large number of neurons after their chronic implantation offer opportunities for understanding neural circuit mechanisms and developing next-generation brain-computer interfaces. The implementation of ultraflexible MEAs requires their reliable implantation into deep brain tissues in a minimally invasive manner, as well as their precise integration with optogenetic tools to enable the simultaneous recording of neural activity and neuromodulation. Here, we describe the process for the preparation of elastocapillary self-assembled ultraflexible MEAs, their use in combination with adeno-associated virus vectors carrying opsin genes and promoters to form an optrode probe and their in vivo experimental use in the brains of rodents, enabling electrophysiological recordings and optical modulation of neuronal activity over long periods of time (on the order of weeks to months). The procedures, including device fabrication, probe assembly and implantation, can be completed within 3 weeks. The protocol is intended to facilitate the applications of ultraflexible MEAs for long-term neuronal activity recording and combined electrophysiology and optogenetics. The protocol requires users with expertise in clean room facilities for the fabrication of ultraflexible MEAs.

Task-specific modulation of corticospinal neuron activity during motor learning in mice

Motor skill learning relies on the plasticity of the primary motor cortex as task acquisition drives cortical motor network remodeling. Large-scale cortical remodeling of evoked motor outputs occurs during the learning of corticospinal-dependent prehension behavior, but not simple, non-dexterous tasks. Here we determine the response of corticospinal neurons to two distinct motor training paradigms and assess the role of corticospinal neurons in the execution of a task requiring precise modulation of forelimb movement and one that does not. In vivo calcium imaging in mice revealed temporal coding of corticospinal activity coincident with the development of precise prehension movements, but not more simplistic movement patterns. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity show the necessity for patterned corticospinal network activity in the execution of precise movements but not simplistic ones. Our findings reveal a critical role for corticospinal network modulation in the learning and execution of precise motor movements.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF=HF diet mice submitted to IF; HF-T=HF diet mice submitted to ET; HF-IFT=HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Fiber-based optrode with microstructured fiber tips for controlled light delivery in optogenetics

Objective. Optogenetic modulation of neuronal activity requires precise and flexible light delivery to deep brain regions. Flat cleaved optical fibers combined with electrodes are widely used in implantable optogenetic devices for light delivery and electrical monitoring of neural activity. However, the flat fiber tip geometry induces serious tissue damage upon insertion, and makes it difficult to adjust and control the spatial extent of illumination within the brain. With their strongly increased tissue-compatibility and the possibility of spatial illumination control, tapered fibers outperform cleaved fibers in targeted neural photo-stimulation. Approach. In this work, we describe our device concept, and present a novel approach for reproducible fabrication of tapered fiber tips via grinding. Furthermore, we characterize recording electrodes by commenting data obtained from electrochemical impedance spectroscopy (EIS). We also investigate the impact of different cone angles (14°, 30°, 60°, and 90°) on the illumination profile and optical throughput. Main results. We fabricated a fiber-based optrode with cone tip and two deposited electrodes. Custom grinding setup for fabrication of tapered fiber tips with various cone angles is developed as a part of our research. Microscope images showed very good optical quality of cone tips. The results of transmitted optical power measurements performed with integrating sphere suggest that, compared to the flat cleaved optical fiber, transmitted power decreases exponentially with cone angle reduction. Obtained emission profiles (as induced fluorescence in Rhodamine 6G water solution) indicate very strong effect of cone angle on shape and size of illumination volume. Results obtained from EIS show the effect of electrode size on its recording capability. Significance. Compared to optrodes with flat cleaved optical fiber, the demonstrated fiber-based optrode with cone tip allows controlled light delivery with reduced invasiveness. The possibility to fabricate reproducible fiber tips with various cone angles enables control of light delivery in optogenetic experiment. The results presented here give neuroscientists the possibility to choose the appropriate tissue-compatible cone geometry depending on their stimulation requirements.