Biomedical subjects

D Kleinfeld

Publications and source records attributed to D Kleinfeld.

At least 19 recordsLinked to original sources

PubMed2000

Direct evidence for local oscillatory current sources and intracortical phase gradients in turtle visual cortex.

Visual stimuli induce oscillations in the membrane potential of neurons in cortices of several species. In turtle, these oscillations take the form of linear and circular traveling waves. Such waves may be a consequence of a pacemaker that emits periodic pulses of excitation that propagate across a network of excitable neuronal tissue or may result from continuous and possibly reconfigurable phase shifts along a network with multiple weakly coupled neuronal oscillators. As a means to resolve the origin of wave propagation in turtle visual cortex, we performed simultaneous measurements of the local field potential at a series of depths throughout this cortex. Measurements along a single radial penetration revealed the presence of broadband current sources, with a center frequency near 20 Hz (gamma band), that were activated by visual stimulation. The spectral coherence between sources at two well-separated loci along a rostral-caudal axis revealed the presence of systematic timing differences between localized cortical oscillators. These multiple oscillating current sources and their timing differences in a tangential plane are interpreted as the neuronal activity that underlies the wave motion revealed in previous imaging studies. The present data provide direct evidence for the inference from imaging of bidirectional wave motion that the stimulus-induced electrical waves in turtle visual cortex correspond to phase shifts in a network of coupled neuronal oscillators.

Animals↗

PubMed1999

Dendritic Ca(2+)-activated K(+) conductances regulate electrical signal propagation in an invertebrate neuron.

Activity-dependent changes in the short-term electrical properties of neurites were investigated in the anterior pagoda (AP) cell of leech. Imaging studies revealed that backpropagating Na(+) spikes and synaptically evoked EPSPs caused Ca(2+) entry through low-voltage-activated Ca(2+) channels that are distributed throughout the neurites. Voltage-clamp recordings from the soma revealed a TEA-sensitive outward current that was reduced when Ca(2+) entry was blocked with Co(2+) or when the intracellular concentration of free Ca(2+) was reduced by a high-affinity Ca(2+) buffer. Ca(2+) released in the neurite from a caged Ca(2+) compound caused a hyperpolarization of the membrane potential. These data imply that the AP cell expresses Ca(2+)-activated K(+) conductances, and that these conductances are present in the neurites. When the Ca(2+)-activated K(+) current was reduced through the block of Ca(2+) entry, backpropagating Na(+) spikes and synaptically evoked EPSPs increased in amplitude. Hence, the activity-dependent changes in the intracellular [Ca(2+)] together with the Ca(2+)-activated K(+) conductances participate in the regulation of dendritic signal propagation.

Action Potentials↗

PubMed1999

Ultra-miniature headstage with 6-channel drive and vacuum-assisted micro-wire implantation for chronic recording from the neocortex.

We describe a head-stage, with precision microtranslators for the chronic placement of micro-wire electrodes in the neocortex, that minimizes compressive damage to the brain. The head-stage has a diameter of 5.8 mm and allows six electrodes, separated by 450 microm on a hexagonal grid, to be individually and continuously positioned throughout a depth of approximately 3 mm. Suction is used to transiently support the dura against a curved array of tubes that guide and stabilize the electrodes as a means to prevent compression of the neocortex as the electrodes breach the dura. With this headstage we recorded extracellular signals in a rat immediately after surgery. Single-unit waveforms at a given electrode position were stable for at least several hours in the freely behaving animal and were obtained throughout the depth of the neocortex for at least 2 months. Electrophysiological records and histological examination showed that the upper layers of the neocortex were intact and minimally damaged after the implantation.

Animals↗

PubMed1999

Supralinear summation of synaptic inputs by an invertebrate neuron: dendritic gain is mediated by an "inward rectifier" K(+) current.

Dendritic processing of glutamatergic synaptic inputs was investigated in the anterior pagoda cell of leech. We observed that below spike threshold, the amplitude of individual EPSPs decreased with hyperpolarization and that simultaneous stimulation of pairs of synaptic inputs leads to the supralinear summation of EPSPs. Voltage-clamp measurements revealed a hyperpolarization-activated, Ba(2+)-sensitive, fast, noninactivating K(+) conductance that depends on the external [K(+)]. These features are those of an "inward rectifier," Kir. Microsurgery experiments, in combination with electrophysiological measurements, revealed an inhomogeneous spatial distribution of the Kir conductance. Furthermore, on surgical removal of the neurites that contain the Kir conductance, the amplitude of EPSPs from the remaining synaptic inputs increased with hyperpolarization. A model cell, with the Kir conductance as the sole voltage-dependent conductance, reproduced qualitatively the observed voltage dependence of individual EPSPs as well as the supralinear summation of EPSP pairs.

2-Amino-5-phosphonovalerate↗

PubMed1999

Identification of neural circuits by imaging coherent electrical activity with FRET-based dyes.

We show that neurons that underlie rhythmic patterns of electrical output may be identified by optical imaging and frequency-domain analysis. Our contrast agent is a two-component dye system in which changes in membrane potential modulate the relative emission between a pair of fluorophores. We demonstrate our methods with the circuit responsible for fictive swimming in the isolated leech nerve cord. The output of a motor neuron provides a reference signal for the phase-sensitive detection of changes in fluorescence from individual neurons in a ganglion. We identify known and possibly novel neurons that participate in the swim rhythm and determine their phases within a cycle. A variant of this approach is used to identify the postsynaptic followers of intracellularly stimulated neurons.

Animals↗

PubMed1999

Anatomical loops and their electrical dynamics in relation to whisking by rat.

An accumulation of anatomical, behavioral, and electrophysiological evidence allows us to identify the neuronal circuitry that is involved with vibrissa-mediated sensation and the control of rhythmic vibrissa movement. Anatomical evidence points to a multiplicity of closed sensorimotor loops, while electrophysiological data delineate the flow of electrical signals in these pathways. These loops process sensory input from the vibrissae and send projections to direct vibrissa movement, starting at the level of the hindbrain and proceeding toward loops that involve multiple structures in the forebrain. The nature of the vibrissa-related electrical signals in behaving animals has been studied extensively at the level of neocortical loops. Two types of spike signal are observed that serve as a reference of vibrissa motion: a fast signal that correlates with the relative phase of the vibrissae within a whisk cycle and a slow signal that correlates with the amplitude, and possibly the set-point, of the vibrissae during a whisk. Both signals are observed in vibrissa primary sensory (S1) cortex, and in some cases they are sufficiently robust to allow vibrissa position to be accurately estimated from the spike train of a single neuron. Unlike the case for S1 cortex, only the slow signal has been observed in vibrissa primary motor (M1) cortex. The control capabilities of M1 cortex were estimated from experiments with anesthetized animals in which progressive areas along the vibrissa motor branch were microstimulated with rhythmically applied currents. The motion of the vibrissae followed stimulation of M1 cortex only for rates that were well below the frequency of rhythmic whisking; in contrast, the vibrissae followed stimulation of the facial nucleus, whose cells directly drive the vibrissae, for rates above that of whisking. In toto, the evidence implies that there is fast signaling from the facial nucleus, through the mystacial pad and the vibrissae and up through sensory cortex, but only slow signaling at the level of the motor cortex and down through the superior colliculus to the facial nucleus. The transformation from fast sensory signals to slow motor control is an unresolved issue. On the other hand, there is a candidate scheme to understand how the fast reference of vibrissa motion in the whisk cycle may be used to decode the angle of the vibrissae upon their contact with an object. We discuss a circuit in which servo mechanisms are used to determine the angle of contact relative to the preferred phase of the fast reference signals. Support for this scheme comes from results with anesthetized animals on the frequency and phase entrainment of intrinsic neuronal oscillators in S1 cortex. A prediction based on this scheme is that the output from a decoder circuit is maximal when the angle of contact differs from the preferred phase of a fast regerence signal. In contrast, for correlation-based schemes the output is maximal when the angle of contact equals the preferred phase.

Animals↗

PubMed1998

Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex.

Cortical blood flow at the level of individual capillaries and the coupling of neuronal activity to flow in capillaries are fundamental aspects of homeostasis in the normal and the diseased brain. To probe the dynamics of blood flow at this level, we used two-photon laser scanning microscopy to image the motion of red blood cells (RBCs) in individual capillaries that lie as far as 600 micrometers below the pia mater of primary somatosensory cortex in rat; this depth encompassed the cortical layers with the highest density of neurons and capillaries. We observed that the flow was quite variable and exhibited temporal fluctuations around 0.1 Hz, as well as prolonged stalls and occasional reversals of direction. On average, the speed and flux (cells per unit time) of RBCs covaried linearly at low values of flux, with a linear density of approximately 70 cells per mm, followed by a tendency for the speed to plateau at high values of flux. Thus, both the average velocity and density of RBCs are greater at high values of flux than at low values. Time-locked changes in flow, localized to the appropriate anatomical region of somatosensory cortex, were observed in response to stimulation of either multiple vibrissae or the hindlimb. Although we were able to detect stimulus-induced changes in the flux and speed of RBCs in some single trials, the amplitude of the stimulus-evoked changes in flow were largely masked by basal fluctuations. On average, the flux and the speed of RBCs increased transiently on stimulation, although the linear density of RBCs decreased slightly. These findings are consistent with a stimulus-induced decrease in capillary resistance to flow.

Animals↗

PubMed1998

Charge displacements in interfacial layers containing reaction centers.

Reaction centers from the photosynthetic bacterium Rhodobacter sphaeroides were oriented in phospholipid interfacial layers adsorbed to a Teflon film separating two electrolyte-filled compartments of a Teflon cell. Light-induced voltage changes were measured as a function of time across electrodes immersed in the cell compartments. The experimental system is characterized both experimentally and theoretically to relate the measured signals to the light-induced displacement currents in the reaction centers. Mathematical relations between the measured signals and the distances and geometries of the charge-transfer reactions are derived. At pH 8.0 the reaction centers were found to be oriented with approximately 60% of the population oriented with the donor facing the aqueous phase. The density of the reaction centers in the layer was approximately 10(11) cm-2, which is close to that found in the native system. Reconstitution of the secondary quinone, QB, in 90% of the RCs was achieved with an approximately 100-fold excess of ubiquinone in the vesicle preparation.

Electrochemistry↗

PubMed1998

Voltage-sensitive dyes for monitoring multineuronal activity in the intact central nervous system.

Optical monitoring of activity provides new kinds of information about brain function. Two examples are discussed in this article. First, the spike activity of many individual neurons in small ganglia can be determined. Second, the spatiotemporal characteristics of coherent activity in the brain can be directly measured. This article discusses both general characteristics of optical measurements (sources of noise) as well as more methodological aspects related to voltage-sensitive dye measurements from the nervous system.

Action Potentials↗

PubMed1997

Visual stimuli induce waves of electrical activity in turtle cortex.

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334-337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of approximately pi/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Animals↗

PubMed1997

In vivo dendritic calcium dynamics in neocortical pyramidal neurons.

The dendrites of mammalian pyramidal neurons contain a rich collection of active conductances that can support Na+ and Ca2+ action potentials (for a review see ref. 1). The presence, site of initiation, and direction of propagation of Na+ and Ca2+ action potentials are, however, controversial, and seem to be sensitive to resting membrane potential, ionic composition, and degree of channel inactivation, and depend on the intensity and pattern of synaptic stimulation. This makes it difficult to extrapolate from in vitro experiments to the situation in the intact brain. Here we show that two-photon excitation laser scanning microscopy can penetrate the highly scattering tissue of the intact brain. We used this property to measure sensory stimulus-induced dendritic [Ca2+] dynamics of layer 2/3 pyramidal neurons of the rat primary vibrissa (Sm1) cortex in vivo. Simultaneous recordings of intracellular voltage and dendritic [Ca2+] dynamics during whisker stimulation or current injection showed increases in [Ca2+] only in coincidence with Na+ action potentials. The amplitude of these [Ca2+] transients at a given location was approximately proportional to the number of Na+ action potentials in a short burst. The amplitude for a given number of action potentials was greatest in the proximal apical dendrite and declined steeply with increasing distance from the soma, with little Ca2+ accumulation in the most distal branches, in layer 1. This suggests that widespread Ca2+ action potentials were not generated, and any significant [Ca2+] increase depends on somatically triggered Na+ action potentials.

Animals↗

PubMed1997

Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices.

The computations performed within cortex are likely to be determined by its internal dynamics in addition to its pattern of afferent input. As a step toward characterizing these dynamics, we have imaged electrical activity in slices from rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In response to electrical stimulation two fluorescence signals of similar maximum amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is dependent on membrane voltage, and has a significant presynaptic component. This signal can be used to image electrical activity ratiometrically. (ii) A slow signal that peaks a few seconds after stimulation, does not reflect voltage changes, and may originate from changes in scattering properties of the slice and from interactions of the dye with the cells. The spatial pattern of fast signals obtained in response to focal stimulation of coronal slices is consistent with known interlaminar projection patterns. In tangential slices, imaging of fast signals reveals clustered horizontal responses. Finally, imaging of fast signals during epileptiform activation of the disinhibited circuit reveals propagating responses, without evidence for modular activation.

Animals↗

PubMed1997

Central versus peripheral determinants of patterned spike activity in rat vibrissa cortex during whisking.

We report on the relationship between single-unit activity in primary somatosensory vibrissa cortex of rat and the rhythmic movement of vibrissae. Animals were trained to whisk freely in air in search of food. Electromyographic (EMG) recordings from the mystatial pads served as a reference for the position of the vibrissae. A fast, oscillatory component in single-unit spike trains is correlated with vibrissa position within the whisk cycle. The phase of the correlation for different units is broadly distributed. A second, slowly varying component of spike activity correlates with the amplitude of the whisk cycle. For some units, the phase and amplitude correlations were of sufficient strength to allow the position of the whiskers to be accurately predicted from a single spike train. To determine whether the observed patterned spike activity was driven by motion of the vibrissae, as opposed to central pathways, we reversibly blocked the contralateral facial motor nerve during the behavioral task so that the rat whisked only on the ipsilateral side. The ipsilateral EMG served as a reliable reference signal. The fast, oscillatory component of the spike-EMG correlation disappears when the facial motor nerve is blocked. This implies that the position of vibrissae within a cycle is encoded through direct sensory activation. The slowly varying component of the spike-EMG correlation is unaffected by the block. This implies that the amplitude of whisking is likely to be mediated by corollary discharge. Our results suggest that motor cortex does not relay a reference signal to sensory cortex for positional information of the vibrissae during whisking.

Action Potentials↗

PubMed1996

Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes.

We have identified large-scale patterns of electrical activity in circuits that occur in response to stimulation of peripheral receptors. Our focus was on primary (S1) vibrissal cortex of anesthetized rat, and we used optical techniques in conjunction with voltage-sensitive dyes to measure depolarization of the upper layers of cortex. Displacement of one vibrissa produced a field of activity that extends over very many cortical columns in S1. There are multiple, focal maxima within this field. A global maximum is located near the center of the field of activity, and, as determined electrically and histologically, this site maps to the cortical column appropriate for the deflected vibrissa. The amplitude of this component attains a steady-state value under continuous stimulation. Additional temporal characteristics are revealed by the response to a single displacement; the signal was triphasic and began with a prompt depolarization that was followed by a transient phase of inhibition and a final phase of long-lasting depolarization. The somatotopy of the other, satellite maxima in the field of activity were established through the reconstruction of the fields of activity produced by individual stimulation of other vibrissae. Local maxima for one vibrissa were seen to overlie the global maximum found for stimulation of nearest- and next-nearest-neighbor vibrissae. In contrast to the amplitude of the global maxima, the amplitude associated with the local maxima was not maintained with either continuous or infrequent but repetitive stimulation. Finally, the field of activity induced by alternate deflection of two neighboring vibrissae was suppressed in amplitude in comparison to the summed amplitudes of the signals elicited by deflection of each vibrissa alone. We suggest that these patterns of activity are a manifestation of the dynamic interaction among neighboring cortical columns.

Adaptation, Physiological↗

PubMed1996

Oscillations and gaseous oxides in invertebrate olfaction.

Olfactory systems combine an extraordinary molecular sensitivity with robust synaptic plasticity. Central neuronal circuits that perform pattern recognition in olfaction typically discriminate between hundreds of molecular species and form associations between odor onsets and behavioral contingencies that can last a lifetime. Two design features in the olfactory system of the terrestrial mollusk Limax maximus may be common elements of olfactory systems that display the twin features of broad molecular sensitivity and rapid odor learning: spatially coherent oscillations in the second-order circuitry that receives sensory input; and involvement of the interneuronal messengers nitric oxide (NO) and carbon monoxide (CO) in sensory responses and circuit dynamics of the oscillating olfactory network. The principal odor processing center in Limax, the procerebrum (PC) of the cerebral ganglion, contains on the order of 10(5) local interneurons and receives both direct and processed input from olfactory receptors. Field potential recordings in the PC show an oscillation at approximately 0.7 Hz that is altered by odor input. Optical recordings of voltage changes in local regions of the PC show waves of depolarization that originate at the distal pole and propagate to the base of the PC. Weak odor stimulation transiently switches PC activity from a propagating mode to a spatially uniform mode. The field potential oscillation in the PC lobe depends on intercellular communication via NO, based on opposing effects of reagents that decrease or increase NO levels in the PC. Inhibition of NO synthase slows the field potential oscillation, while application of exogenous NO increases the oscillation frequency. A role for CO in PC dynamics is suggested by experiments in which CO liberation increases the PC oscillation frequency. These design features of the Limax PC lobe odor processing circuitry may relate to synaptic plasticity that subserves both connection of new receptors throughout the life of the slug and its highly developed odor learning ability.

Animals↗

PubMed1996

Automatic sorting of multiple unit neuronal signals in the presence of anisotropic and non-Gaussian variability.

Neuronal noise sources and systematic variability in the shape of a spike limit the ability to sort multiple unit waveforms recorded from nervous tissue into their single neuron constituents. Here we present a procedure to efficiently sort spikes in the presence of noise that is anisotropic, i.e., dominated by particular frequencies, and whose amplitude distribution may be non-Gaussian, such as occurs when spike waveforms are a function of interspike interval. Our algorithm uses a hierarchical clustering scheme. First, multiple unit records are sorted into an overly large number of clusters by recursive bisection. Second, these clusters are progressively aggregated into a minimal set of putative single units based on both similarities of spike shape as well as the statistics of spike arrival times, such as imposed by the refractory period. We apply the algorithm to waveforms recorded with chronically implanted micro-wire stereotrodes from neocortex of behaving rat. Natural extension of the algorithm may be used to cluster spike waveforms from records with many input channels, such as those obtained with tetrodes and multiple site optical techniques.

Action Potentials↗

PubMed1996

Central and reflex neuronal responses elicited by odor in a terrestrial mollusk.

1. We studied the responses to odor of a central olfactory processing organ and subsequent central outputs in the terrestrial mollusk Limax maximus. We used extracellular recording techniques and optical recording from preparations stained with a voltage-sensitive dye to characterize network responses in the central organ and whole nerve recording to characterize central odor-elicited outputs. 2. The central olfactory organ, the procerebral (PC) lobe, is a highly interconnected network of local olfactory interneurons that receives input from primary olfactory receptors. In the absence of odor the PC network is known to exhibit periodic waves of excitation and inhibition at a frequency of approximately 0.7 Hz. Here we study how different odor inputs affect the intrinsic oscillatory dynamics. 3. Odor stimulation causes the propagation of electrical activity along the lobe to transiently switch from the state with propagating waves, with typical phase shifts of one half cycle along the lobe, to a state with few or no phase differences along the lobe. The collapse of the phase gradient typically occurs without spatially localized changes in the amplitude of the oscillation, at least on the scale of our optical resolution, approximately 0.1 times the length of the lobe. In some trials, however, we resolved spatial nonuniformities in the magnitude of excitation across the lobe. 4. The collapse of the phase gradient along the lobe in response to odor stimulation is robust on a trial-by-trial basis. Further, the change in phase gradient can occur with little or no change in the frequency of oscillation, as occasionally observed in response to weak odor stimulation. 5. Typically odor stimulation causes changes in the frequency of the oscillation. Two odors, one attractive (potato) and one repellent (amyl acetate), produced different patterns of change; potato induced a transient increase in frequency, whereas amyl acetate produced an initial decrease in frequency followed by a transient increase in frequency. We do not yet know whether these frequency change patterns are unique to these specific odors or to their behavioral meaning. 6. Previous work demonstrated direct connections from the PC lobe to the buccal and pedal ganglia, centers controlling feeding and locomotion, respectively. To establish a correlation between odor-induced changes in the PC lobe and activation of such centers and subsequently effector organs, we recorded from selected central connectives and peripheral nerve roots. The dependence of odor-elicited activity recorded in connectives and nerve roots on PC integrity was assessed by measurements of odor-elicited activity before and after PC ablation. 7. Odor stimulation caused activation of multiple units in the cerebrobuccal connective. One output of the buccal ganglion, the salivary nerve, also showed odor-elicited activation of an identified unit, the slow burster. The necessity of the PC lobe for activation of the slow burster was established by measurements of odor-elicited activity before and after PC ablation. 8. Odor stimulation also caused activation of multiple units in the buccal mass retractor nerve. Activation of a fraction of these units (3 of 10) was dependent on an intact PC lobe, like the slow burster neuron in the salivary nerve. 9. Our results clearly show how stimuli may lead to changes in the spatial-temporal pattern of activity in a central circuit without changing the overall average level of activity in that circuit.

Animals↗

PubMed1996

Variability of extracellular spike waveforms of cortical neurons.

1. Here we study the variability in extracellular records of action potentials. Our work is motivated, in part, by the need to construct effective algorithms to classify single-unit waveforms from multiunit recordings. 2. We used microwire electrode pairs (stereotrodes) to record from primary somatosensory cortex of awake, behaving rat. Our data consist of continuous records of extracellular activity and segmented records of extracellular spikes. Spectral and principal component techniques are used to analyze mean single-unit wave-forms, the variability between different instances of a single-unit waveform, and the underlying background activity. 3. The spectrum of the variability between different instances of a single-unit waveforms is not white, and falls off above 1 kHz with a frequency dependence of roughly f-2. This spectrum is different from that of the mean spike waveforms, which falls off roughly as f-4, but is essentially identical with the spectrum of background activity. The spatial coherence of the variability on the 10-micron scale also falls off at high frequencies. 4. The variability between different instances of a single-unit waveform is dominated by a relatively small number of principal components. As a consequence, there is a large anisotropy in the cluster of the spike waveforms. 5. The background noise cannot be represented as a stationary Gaussian random process. In particular, we observed that the spectrum changes significantly between successive 20-ms intervals. Furthermore, the total power in the background activity exhibits larger fluctuations than is consistent with a stationary Gaussian random process. 6. Roughly half of the single-unit spike waveforms exhibit systematic changes as a function of the interspike interval. Although this results in a non-Gaussian distribution in the space of waveforms, the distribution can be modeled by a scalar function of the interspike interval. 7. We use a set of 44 mean single-unit waveforms to define the space of differences between spike waveforms. This characterization, together with that of the background activity, is used to construct a filter that optimizes the detection of differences between single-unit waveforms. Further, an information theoretic measure is defined that characterizes the detectability.

Action Potentials↗