Unexceptional sharpness of frequency tuning in the human cochlea

The responses to sound of auditory-nerve fibers are well known in many animals but are topics of conjecture for humans. Some investigators have claimed that the auditory-nerve fibers of humans are more sharply tuned than are those of various experimental animals. Here we invalidate such claims. First, we show that forward-masking psychophysical tuning curves, which were used as the principal support for those claims, greatly overestimate the sharpness of cochlear tuning in experimental animals and, hence, also probably in humans. Second, we calibrate compound action potential tuning curves against the tuning of auditory-nerve fibers in experimental animals and use compound action potential tuning curves recorded in humans to show that the sharpness of tuning in human cochleae is not exceptional and that it is actually similar to tuning in all mammals and birds for which comparisons are possible. Third, we note that the similarity of frequency of tuning across species with widely diverse cochlear lengths and auditory bandwidths implies that for any given stimulus frequency the "cochlear amplifier" is confined to a highly localized region of the cochlea.     

Plasticity and tuning by visual feedback of the stability of a neural integrator

Persistent neural firing is of fundamental importance to working memory and other brain functions because it allows information to be held "online" following an input and to be integrated over time. Many models of persistent activity rely on some kind of positive feedback internal to the neural circuit concerned; however, too much feedback causes runaway firing (instability), and too little results in loss of persistence (leak). This parameter sensitivity leads to the hypothesis that the brain uses an error signal (external feedback) to tune the stability of persistent firing by adjusting the amount of internal feedback. We test this hypothesis by manipulating external visual feedback, a putative sensory error signal, in a model system for persistent firing, the goldfish oculomotor neural integrator. Over tens of minutes to hours, electronically controlled visual feedback consistent with a leaky or unstable integrator can drive the integrator progressively more unstable or leaky, respectively. Eye fixation time constants can be reduced >100-fold to <1 s. Normal visual feedback gradually retunes the integrator back to stability. Changes in the phase of the sinusoidal vestibulo-ocular response are consistent with integrator detuning, as are changes in ocular drift following eye position shifts compensating for brief passive head movements during fixations. Corresponding changes in persistent firing of integrator neurons are presented in the accompanying article. The presence, strength, and reversibility of the plasticity demonstrate that, in this system, external visual feedback plays a vital role in gradually tuning the stability of the neural integrator.     

Plasticity and tuning of the time course of analog persistent firing in a neural integrator

In a companion paper, we reported that the goldfish oculomotor neural integrator could be trained to instability or leak by rotating the visual surround with a velocity proportional to +/- horizontal eye position, respectively. Here we analyze changes in the firing rate behavior of neurons in area I in the caudal brainstem, a central component of the oculomotor neural integrator. Persistent firing could be detuned to instability and leak, respectively, along with fixation behavior. Prolonged training could reduce the time constant of persistent firing of some cells by more than an order of magnitude, to <1 s. Normal visual feedback gradually retuned persistent firing of integrator neurons toward stability, along with fixation behavior. In animals with unstable fixations, approximately half of the eye position-related cells had upward or unstable firing rate drift. In animals with leaky fixations, two-thirds of the eye position-related cells showed leaky firing drift. The remaining eye position-related cells, generally those with lower eye position thresholds, showed a more complex pattern of history-dependent/predictive firing rate drift in relation to eye drift. These complex drift cells often showed a drop in maximum persistent firing rate after training to leak. Despite this diversity, firing drift and the degree of instability or leak in firing rates were broadly correlated with fixation performance. The presence, strength, and reversibility of this plasticity demonstrate that, in this system, visual feedback plays a vital role in gradually tuning the time course of persistent neural firing.     

Mechanical restitution and post extrasystolic potentiation of perfused rat heart: quantitative comparison of normal right and left ventricular responses.

Interval-force relationship of right and left ventricles of the isolated perfused rat heart was quantified by fitting polynomial, linear and mixed linear-exponential functions to the mechanical restitution (MRC) and post extrasystolic potentiation (PESPC) curves. Ventricular maximum developed pressure (Pmax) and its first derivative (dP/dtmax) were used as indices of contractility. MRCs and PESPCs could be separated into two distinct phases: phase A and phase B of MRCs; phase I and phase II of PESPCs. These phases for the right and left ventricle of the rat heart could be explained on the same model of cellular kinetics of the activator calcium, but showed distinct differences from other species. Right and left ventricle inotropic reserve (CRmax), as quantified from the centre of mass of the phase B of MRCs (from normalized Pmax), was (mean +/- SE): 132.4 +/- 2.05% and 132.1 +/- 1.7% at 1 Hz, which increased significantly (P less than 0.001) to 181.0 +/- 5.8% and 182.3 +/- 5.2% at 3.3 Hz, respectively. Linear regression of normalized right ventricle extrasystolic responses on the left ventricle responses gave a high correlation coefficient (typically r2 = 0.97). Time constants of the fitted mechanical restitution (TMRC) and post extrasystolic potentiation (TPESPC) curves were at 1 Hz, TMRC and TPESPC (from normalized dP/dtmax) were (mean +/- SE): 161.6 +/- 10.8 and 159.0 +/- 13.2 ms for right ventricle, and 196.1 +/- 14.5 and 188.3 +/- 10.7 ms for left ventricle, respectively. The results of this study indicate that interval-force relationship of the rat heart, as exemplified by CRmax and time constants of the fitted curves, could provide a useful index for quantifying and comparing right and left ventricular functions.     

Mechanical properties of the colon: comparison of the features of the African and European colon in vitro.

The tensile properties of the colon have been examined using methods which gave repeatable results. They showed little change after storage in salt for up to five weeks. The burst strength remained unchanged along the length of the colon. The tensile strength fell distally, as the thickness of the colonic wall increased. The width at burst decreased distally as did the internal diameter. The visco-elastic property of stress relaxation was constant in all regions. The tensile property of the colon was well developed at birth, but fell with age as did the width at burst and the internal diameter. Stress relaxation was unaffected. Because there may be a mechanical abnormality of the colonic wall in diverticular disease and as Europeans are prone to this condition while Africans are not commonly affected, European and African colons were compared. The tensile strength in a Kampala group was greater than in an Edinburgh one, but fell significantly in both groups with age. The width at burst was greater in the Kampala group, but also declined with age. Stress-relaxation was similar in both groups. In view of the similar properties in childhood of colons from Edinburgh and Kampala, the strength of the adult African compared with European colons may derive later from environmental factors such as diet. There were, however, no differences between the colons with and without diverticular disease in European subjects over the age of 50 years.     

Brief Report: Spatial tuning of electrophysiological responses to multisensory stimuli reveals a primitive coding of the body boundaries in newborns

The ability to identify our own body and its boundaries is crucial for survival. Ideally, the sooner we learn to discriminate external stimuli occurring close to our body from those occurring far from it, the better (and safer) we may interact with the sensory environment. However, when this mechanism emerges within ontogeny is unknown. Is it something acquired throughout infancy, or is it already present soon after birth? The presence of a spatial modulation of multisensory integration (MSI) is considered a hallmark of a functioning representation of the body position in space. Here, we investigated whether MSI is present and spatially organized in 18- to 92-h-old newborns. We compared electrophysiological responses to tactile stimulation when concurrent auditory events were delivered close to, as opposed to far from, the body in healthy newborns and in a control group of adult participants. In accordance with previous studies, adult controls showed a clear spatial modulation of MSI, with greater superadditive responses for multisensory stimuli close to the body. In newborns, we demonstrated the presence of a genuine electrophysiological pattern of MSI, with older newborns showing a larger MSI effect. Importantly, as for adults, multisensory superadditive responses were modulated by the proximity to the body. This finding may represent the electrophysiological mechanism responsible for a primitive coding of bodily self boundaries, thus suggesting that even just a few hours after birth, human newborns identify their own body as a distinct entity from the environment.     

The scientific bases of cancer management: at the interface between fundamental research and clinical practice

Summary From 1950 to 1985 the 5-year survival rate of cancer patients in industrialized countries, has slowly increased from 25% in 1950 to 50% in 1985. This progress has been due to earlier diagnosis and to a gradual improvement of treatment modalities. Clinical needs have stimulated basic research and clinical investigation. In turn, biological research has introduced new concepts and new agents. Clinical investigation and applied research have brought about an improvement in therapeutic methods and a better understanding of the growth and progression of human cancers which has, in particular, led to the concept of adjuvant treatment of occult metastases. The major recent breakthroughs in fundamental research have reinforced the value of close cooperation between clinicians and fundamentalists. Most of the new biologic tools are specific and only active on tumors cells with well-defined characteristics. Furthermore some new techniques such as adoptive immunotherapy can induce complete tumor regression in some patients and have no detectable effects in other patients with apparently similar tumors. Some cytokines have different effects on experimental and human tumors. The cytokine network is so complex that the administration of one of them can induce unpredictable effects. It has been recognized that experimental tumors and in vitro studies can be misleading and there is no substitute for clinical studies on patients. Moreover clinical experience has documented the amazing ability of tumors to become resistant to all these new agents. Numerous new therapeutic methods are being explored, however with the current state of knowledge it appears that although they can help to control tumors, they still fail to eradicate them. We must therefore learn how to integrate them with conventional therapies. Advances in therapy shall be achieved only by well-designed clinical trials. Thus at the interface between fundamental research and clinical practice there is an urgent need for oncologists with a strong scientific background and laboratory scientists with a deep interest in clinical investigations.Abbreviations MOPP mechlorethamine, vincrestine, procarbazine, prednimurtine - ABVD Adrianycin, bleomycin, vinblastine, dacarbazine - CEA carcinoembryonic antigen - CT chemotherapy - RT radiotherapy - EGFr epidermal growth factor receptor - ER, PR estrogen and progesterone receptors - CSF colony-stimulating factor The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author The EditorsHarold Dorn Memorial Lecture held at the closing ceremony of the International Congress of Cancer, Hamburg, August 1990     

Pancreatic secretory responses in L-arginine-induced pancreatitis: comparison of diabetic and nondiabetic rats.

The aim of this work was to study cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion after the induction of pancreatitis with L-arginine (ARG) in rats with or without streptozotocin (STZ) diabetes. One, 3, 7, and 14 days after pancreatitis induction, rats were surgically prepared with pancreatic duct and femoral vein cannulae under urethane anesthesia. Graded doses of CCK-8 ranging from 9 to 2,400 ng/kg/30 min were administered intravenously. In the control group, the step-wise increasing doses of CCK-8 resulted in a characteristic dose-response curve for the pancreatic volume, protein and amylase secretion (maximal volume, protein and amylase output at 600 ng/kg/30 min of CCK-8: 157 +/- 20.2 microl/30 min, 28.3 +/- 1.18 mg/30 min, and 3,750 +/- 92 IU/30 min, respectively). In rats with pancreatitis, the pancreatic volume (both basal and maximal) and amylase secretion were significantly elevated on day 1 versus the control group; then on days 3,7, and 14, the pancreatic secretory volume and amylase were progressively and significantly decreased versus the control group. However, the protein output was continuously decreased versus the control group on days 1, 3, 7, and 14. In diabetic rats, the maximal volume and protein and amylase output were all significantly decreased versus the control group throughout the experiment. In the diabetes + pancreatitis group, the maximal volume and protein and amylase output were all significantly increased versus the diabetes group on days 1, 3, 7, and 14. These results indicate that in the early phase of ARG-induced pancreatitis, the pancreatic secretion is characterized by increases in secretory volume and amylase, with a simultaneous decrease in protein output. Simultaneous diabetes seems to moderate the CCK-8-stimulated secretory changes in both the early and late phases after ARG-induced pancreatitis.     

Method for the direct comparison of the frequency behavior in QT- and activity-controlled pacemaker systems

A non-invasive method of testing the suitability of an activity-controlled pacemaker system in patients with VVT-programmable systems is presented. The QT-time controlled TX-pacemaker of a 36-year-old patient was programmed into the VVT-mode. Then the activity-controlled pacemaker (Activitrax) was fixed epicutaneously above the pectoral muscles and two stimulation electrodes were applied above the implanted pacer and the tip of the implanted probe. Thus the external could be made to trigger the implanted system. The frequency profile was recorded with identical loads with QT and/or activity control. For both the frequency-adapted pacemaker systems, the direct comparison yields characteristic frequency profiles: a quick frequency increase and decrease of both Activitrax and load, but a delayed frequency profile of the QT-controlled pacer. Different frequency maxima are rendered by the two pacemakers as a function of the load.     

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.     

Strength training-induced responses in older adults: attenuation of descending neural drive with age

Although reductions in resting H-reflex responses and maximal firing frequency suggest that reduced efferent drive may limit muscle strength in elderly, there are currently no reports of V-wave measurements in elderly, reflecting the magnitude of efferent output to the muscle during maximal contraction. Furthermore, it is uncertain whether potential age-related neural deficiencies can be restored by resistance training. We assessed evoked reflex recordings in the triceps surae muscles during rest and maximal voluntary contraction (MVC), rate of force development (RFD), and muscle mass in seven elderly (74 ± 6 years) males before and after 8 weeks of heavy resistance training, contrasted by seven young (24 ± 4 years) male controls. At baseline, m. soleus (SOL) V/M ratio (0.124 ± 0.082 vs. 0.465 ± 0.197, p < 0.05) and H/M ratio (0.379 ± 0.044 vs. 0.486 ± 0.101 p = 0.07) were attenuated in elderly compared to young. Also, SOL H-reflex latency (33.29 ± 2.41 vs. 30.29 ± 0.67 ms, p < 0.05) was longer in elderly. The reduced neural drive was, despite similar leg muscle mass (10.7 ± 1.2 vs. 11.5 ± 1.4 kg), mirrored by lower MVC (158 ± 48 vs. 240 ± 54 Nm, p < 0.05) and RFD (294 ± 126 vs. 533 ± 123 Nm s⁻¹, p < 0.05) in elderly. In response to training SOL V/M ratio (0.184 ± 0.092, p < 0.05) increased in the elderly, yet only to a level ∼40 % of the young. This was accompanied by increased MVC (190 ± 70 Nm, p < 0.05) and RFD (401 ± 147 Nm⋅s⁻¹, p < 0.05) to levels of ∼80 % and ∼75 % of the young. H/M ratio remained unchanged. These findings suggest that changes in supraspinal activation play a significant role in the age-related changes in muscle strength. Furthermore, this motor system impairment can to some extent be improved by heavy resistance training.     

Perceptions of e-cigarettes: a comparison of adult smokers and non-smokers in a Mechanical Turk sample

Background: Given plans to extend its regulatory authority to e-cigarettes, the Food and Drug Administration (FDA) urgently needs to understand how e-cigarettes are perceived by the public. Objectives: To examine how smoking status impacts adult perceptions and expectations of e-cigarettes. Methods: We used Mechanical Turk (MTurk), a “crowdsourcing” platform, to rapidly survey a large (n = 796; female = 381; male = 415), diverse sample of adult ever (44%) and never smokers (56%), including ever (28%) and never (72%) users of e-cigarettes. Results: Smokers and non-smokers learned about e-cigarettes primarily through the internet and conversations with others. Ever smokers were more likely than never smokers, and female current smokers were more likely than female former smokers, to have learned about e-cigarettes from point of sale advertising (p’s < 0.05) and to believe that e-cigarettes help smokers quit (ps < 0.05). Among never users of e-cigarettes, current smokers were more likely than never smokers and former smokers to report that they would try e-cigarettes in the future (ps < 0.01). Current smokers’ top reason for wanting to try e-cigarettes was to quit or reduce smoking (56%), while never and former smokers listed curiosity. In contrast, female current smokers’ top reason for not trying e-cigarettes was health and safety concerns (44%) while males were deterred by expense (44%). Conclusions: Adult smokers and non-smokers have different perceptions and expectations of e-cigarettes. Public health messages regarding e-cigarettes may need to be tailored separately for persons with and without a history of using conventional cigarettes. Tailoring messages by gender within smoker groups may also improve their impact.     

Squatting revisited: comparison of haemodynamic responses in normal individuals and heart transplantation recipients.

BACKGROUND--Squatting produces a prompt increase in cardiac output and arterial blood pressure which is accompanied by an immediate decrease in heart rate and forearm vascular resistance. The rise in cardiac output and blood pressure has been attributed to augmented venous return from compression of leg veins, while the decreases in heart rate and forearm vascular resistance are probably due to activation of cardiopulmonary and arterial baroreflexes. Haemodynamic patterns in nine normal men and six heart transplant recipients during 2 min of squatting were examined to determine the role of cardiac innervation in the mediation of these responses. METHODS--Stroke volume was monitored by ensemble averaged thoracic impedance cardiography and blood pressure was determined with an Ohmeda fingertip plethysmograph. These techniques provided continuous measurements which were capable of detecting transient and non-steady state changes. Forearm blood flow was measured with venous occlusion plethysmography. Measurements were obtained after 3 min of quiet standing, immediately after squatting, and at 20, 60, and 120 s of sustained squatting. RESULTS--Both groups exhibited similar increases in stroke volume index (normal individuals 10.5 ml/m2; heart transplant recipients 10.3 ml/m2) and mean arterial pressure (normal individuals 8.5 mm Hg; heart transplant recipients 5.0 mm Hg) which were sustained throughout squatting. Each group also showed an initial decrease in peripheral resistance (normal individuals 3.6 units; heart transplant recipients 7.7 units) followed by a return to baseline values after 20 s. Heart rate decreased in normal individuals (10 beats/min) but was unchanged or minimally increased (2 beats/min) in heart transplant recipients. Forearm vascular resistance was conspicuously decreased in normal individuals (47.8 units) but only minimally (20.9 units) and not significantly in heart transplant recipients. CONCLUSIONS--The major haemodynamic responses to squatting (increased cardiac output and blood pressure) are similar in normal individuals and heart transplant recipients. These responses are primarily due to augmented venous return and are not altered by cardiac denervation. Both groups also exhibited a transient decline in peripheral vascular resistance which is most likely mediated by arterial baroreflexes activated by the acute rise in arterial blood pressure. The absence of a significant decrease in forearm vascular resistance in heart transplant recipients suggests that this response is partially mediated by cardiopulmonary or ventricular baroreflexes or that local forearm flow mediated vasodilatation remains impaired after heart transplantation.     

Physiologic responses to incremental and self-paced exercise in COPD: a comparison of three tests

OBJECTIVES: To investigate cardiorespiratory and dyspnea responses to incremental and self-paced exercise tests in patients with COPD. DESIGN: A prospective within-subject design was used. PATIENTS: Twenty stable subjects (15 men), with a mean (+/- SD) age of 64.0 +/- 7.5 years and moderate-to-severe COPD (ie, mean FEV(1), 0.8 +/- 0.3 L and 28.9 +/- 7.9% predicted) were studied. METHODS: Each subject completed a 6-min walk test (6MWT), an incremental shuttle walking test (ISWT), and a cycle ergometer test (CET), within a 2-week period. The tests were performed at least 24 h apart. Standardized encouragement was utilized in each test with the aim of maximizing performance. Heart rate (HR) and dyspnea were measured each minute throughout the tests, and pulse oximetric saturation (Spo(2)) was measured before and immediately after each test. The distances walked in the 6MWT and ISWT were compared to peak oxygen uptake (Vo(2)) values from the CET. RESULTS: HR increased linearly with increasing workload during the CET and ISWT, but increased alinearly with a disproportionate increase early in the 6MWT. In contrast, dyspnea scores increased linearly during the 6MWT, but increased alinearly with a disproportionate increase late during the CET and ISWT. Peak HR and dyspnea were not significantly different between tests. Spo(2) was significantly lower at the end of both walking tests compared to that at the end of the CET (p < 0.001). The distance walked in both the ISWT and 6MWT were related to peak Vo(2) values on the CET (for both tests, r = 0.73; p < 0.001). CONCLUSIONS: The patterns of response in HR and dyspnea seen during the 6MWT suggest that patients with COPD titrate exertion against dyspnea to achieve a peak tolerable intensity. This strategy is not possible in an externally paced ISWT or CET. However, it is a limited strategy, with performance converging at higher workloads. Similar peak exercise responses were achieved in the 6MWT, ISWT, and CET. Greater oxygen desaturation was observed during the field walking tests, suggesting that both the ISWT and 6MWT are more sensitive than the CET in detecting exercise-induced hypoxemia and in assessing ambulatory oxygen therapy needs.     

Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site

Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents.Recent estimates suggest neurological disorders affect up to 6% of the global population (1). The vast majority of treatments generally involve oral administration of pharmaceuticals. When these fail, alternate therapies can include neurosurgery (e.g., in epilepsy) and electrical stimulation via implanted electrodes [e.g., in Parkinson’s disease (1)]. Pharmaceutical and basic research have identified promising targets and designed potentially efficient drugs for multiple disorders, but such drugs haven’t reached patients because of failure during (pre)clinical tests. There are multiple reasons for such failures. Drugs may be toxic in the periphery (2, 3), they may not cross the blood−brain barrier or they may be pumped back to the blood stream by multidrug transporters (4, 5). However, the critical factor is the fact that they may have deleterious side effects when they penetrate “healthy” regions, affecting physiological functions such as memory and learning (6, 7). In addition, because oral administration will lead to a dilution of the drug in the body, there is often a mismatch between the dose necessary to obtain a therapeutic effect in the region to treat and the maximum dose that nonaffected body regions can support without side effects.Providing the drug past the blood−brain barrier, where and when it is needed, constitutes the ideal solution. Such delivery would solve all of the above-mentioned problems (blood−brain barrier crossing, peripheral toxicity, undesirable side effects in healthy regions, and effective dose). Devices have been successfully designed to deliver drugs locally (8). However, the “where” and “when” issues remain to be addressed. Because clinicians may have several spatially distributed regions to treat, or if the volume of the intended treatment region is large, it is important to have multiple drug delivery sites, which would solve the “where” issue. The “when” issue is more difficult to address, as, ideally, a delivery system should act on demand, when needed (e.g., just before an impending seizure). Because electrophysiological signals can be used to predict incoming pathological events (9), electrical activity should be measured at each delivery site to trigger drug delivery at that specific location. Such local, real-time measurement, and precision delivery, would pave the way for closed-loop, fully automatic, therapeutic devices. Finally, because the size of the region to treat may be small—down to the scale of a single cell—the technology should allow spatial resolution of delivery on the order of micrometers.Interfacing malfunctioning neurological pathways with spatial resolution and signal specificity approaching those of the cell could provide significant advantages to future therapies. Microelectrode recordings of the field potentials generated by neurons (or even neuronal firing itself) have become routine in investigations of brain function and dysfunction (10). Small size of recording sites allows for recording of single neurons, and densely packed sites on minimally invasive electrodes enhance the sampling capacity of the probe (11). Such densely packed probes can be accomplished using conducting polymers, such as poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS), without decreasing the quality of the recordings. Conducting polymer electrodes exhibit inherently low impedance characteristics (more than one order of magnitude lower than bare Au, Pt, and Ir electrodes of similar dimensions at 1 kHz), with the low impedance being attributed partly to the high porosity, giving an increased electrochemical surface area (12–14). Additionally, with their mixed electronic and ionic conductivity and the soft mechanical properties that match those of the neural tissue, conducting polymers are ideally suited to obtain high signal-to-noise ratio recordings at the neural interface (15, 16). Recently, we have demonstrated microelectrode arrays based on PEDOT:PSS electrodes for in vitro recordings of electrophysiological signals from rat brain slices (17). These microelectrodes, fabricated at small size and high density, have enabled a good match with the dimensions of neural networks while maintaining high-resolution neural recordings.We have also demonstrated substance delivery mimicking exocytotic release of neurotransmitters at the neuronal scale by means of the organic electronic ion pump (OEIP) (18, 19). The OEIP uses conducting polymer electrodes to electrophoretically “pump” neurotransmitters through a permselective membrane, enabling high spatiotemporal delivery resolution, without necessitating liquid flow. OEIPs have been used in vitro to trigger cell signaling (18, 20) and to control epileptiform activity in vitro (21), as well as in vivo to effect sensory function (19) and as a therapy for pain in awake animals (22). OEIPs have also been demonstrated in a biosensor-regulated system—on a macroscopic scale—to mimic the chemical-to-electrical-to-chemical signal transduction of neurons (23). However, none of these devices meet the desired requirement to record and deliver drugs at the same site.In this work, we engineered a device able to perform electrical sensing of local field potentials and neurotransmitter delivery at the same site. To achieve this colocalized sensing and delivery, we developed a system consisting of an array of OEIP delivery points, where each delivery point is integrated with a conducting polymer electrode for recording neuronal activity. Each integrated delivery/sensing pixel is at the single-cell scale and mimics the multifunctionality of a biological neuron: Electrical information can be sensed from the local cellular environment, and neuroactive compounds can be delivered diffusively, without liquid flow, at the same location. We report on the development and characterization of this system of “neural pixels,” and we demonstrate its use by delivering the endogenous inhibitory neurotransmitter γ-aminobutyric acid (GABA) to locally affect cells while simultaneously monitoring how the delivery modulates the cells’ firing patterns.