Axonal Conduction Time Research Articles

Visual Corticotectal Neurons in Awake Rabbits: Receptive Fields and Driving Monosynaptic Thalamocortical Inputs.

The superior colliculus receives powerful synaptic inputs from corticotectal neurons in the visual cortex. The function of these corticotectal neurons remains largely unknown due to a limited understanding of their response properties and connectivity. Here, we use antidromic methods to identify corticotectal neurons in awake male and female rabbits, and measure their axonal conduction times, thalamic inputs and receptive field properties. All corticotectal neurons responded to sinusoidal drifting gratings with a nonlinear (nonsinusoidal) increase in mean firing rate but showed pronounced differences in their ON-OFF receptive field structures that we classified into three groups, Cx, S2, and S1. Cx receptive fields had highly overlapping ON and OFF subfields as classical complex cells, S2 had largely separated ON and OFF subfields as classical simple cells, and S1 had a single ON or OFF subfield. Thus, all corticotectal neurons are homogeneous in their nonlinear spatial summation but very heterogeneous in their spatial integration of ON and OFF inputs. The Cx type had the fastest conducting axons, the highest spontaneous activity, and the strongest and fastest visual responses. The S2 type had the highest orientation selectivity, and the S1 type had the slowest conducting axons. Moreover, our cross-correlation analyses found that a subpopulation of corticotectal neurons with very fast conducting axons and high spontaneous firing rates (largely "Cx" type) receives monosynaptic input from retinotopically aligned thalamic neurons. This previously unrecognized fast-conducting thalamic-mediated corticotectal pathway may provide specialized information to superior colliculus and prime recipient neurons for subsequent corticotectal or retinal synaptic input.

Compartmental Differences in Macular Retinal Ganglion Cell Function.

PurposeThe purpose of this study was to investigate local differences of macular retinal ganglion cell (RGC) function by means of the steady-state pattern electroretinogram (SS-PERG).MethodsSS-PERGs were recorded in healthy subjects (n = 43) in response to gratings (1.6 c/deg, 15.63 reversals/s, and 98% contrast) presented on an LED display (800 cd/m2, 12.5 degrees eccentricity at 30 cm viewing distance) partitioned in triangular sectors (inferior [I]; nasal [N]; superior [S]; and temporal [T]) or concentric regions (central [C] and annulus [A]). For each partition, response amplitude (nV), amplitude adaptation (% change over recording time), phase/latency (deg/ms), and oscillatory potentials (OPs) amplitude (root mean square [RMS] nV) were measured. Data were analyzed with Generalized Estimating Equation (GEE) statistics.ResultsAmplitude differed (P < 0.001) between sectors (I: 254 nV; N: 328 nV; S: 275 nV; T: 264 nV; and N>T, I) as well as concentrically (C: 684 nV; A: 323 nV; and C>A). Latency did not differ between sectors (range = 53–54 ms, P = 0.45) or concentrically (range = 51–51 ms, P = 0.7). Adaptation did not differ (P = 0.66) concentrically (C: −19% and A: −22%) but differed (P = 0.004) between sectors (I: +25% and S: −29%). The OP amplitude did not differ (P = 0.5) between sectors (range = 63–73 nV) as well as concentrically (range = 82–90 nV, P = 0.3).ConclusionsAmplitude profiles paralleled RGC densities from histological studies. Adaptation profile suggested greater autoregulatory challenge in the inferior retina. Latency profile may reflect axonal conduction time to the optic nerve head assuming a direct relationship between axon length and its size/velocity. Location-independent OPs may reflect preganglionic activity.Translational RelevanceNormal macular RGC function displays local differences that may be related to local vulnerability in optic nerve disorders.

Comparison of Muscle MEPs From Transcranial Magnetic and Electrical Stimulation and Appearance of Reflexes in Horses.

IntroductionTranscranial electrical (TES) and magnetic stimulation (TMS) are both used for assessment of the motor function of the spinal cord in horses. Muscular motor evoked potentials (mMEP) were compared intra-individually for both techniques in five healthy horses. mMEPs were measured twice at increasing stimulation intensity steps over the extensor carpi radialis (ECR), tibialis cranialis (TC), and caninus muscles. Significance was set at p < 0.05. To support the hypothesis that both techniques induce extracranially elicited mMEPs, literature was also reviewed.ResultsBoth techniques show the presence of late mMEPs below the transcranial threshold appearing as extracranially elicited startle responses. The occurrence of these late mMEPs is especially important for interpretation of TMS tracings when coil misalignment can have an additional influence. Mean transcranial motor latency times (MLT; synaptic delays included) and conduction velocities (CV) of the ECR and TC were significantly different between both techniques: respectively, 4.2 and 5.5 ms (MLTTMS–-MLTTES), and −7.7 and −9.9 m/s (CVTMS-CVTES). TMS and TES show intensity-dependent latency decreases of, respectively, −2.6 (ECR) and −2.7 ms (TC)/30% magnetic intensity and −2.6 (ECR) and −3.2 (TC) ms/30V. When compared to TMS, TES shows the lowest coefficients of variation and highest reproducibility and accuracy for MLTs. This is ascribed to the fact that TES activates a lower number of cascaded interneurons, allows for multipulse stimulation, has an absence of coil repositioning errors, and has less sensitivity for varying degrees of background muscle tonus. Real axonal conduction times and conduction velocities are most closely approximated by TES.ConclusionBoth intracranial and extracranial mMEPs inevitably carry characteristics of brainstem reflexes. To avoid false interpretations, transcranial mMEPs can be identified by a stepwise latency shortening of 15–20 ms when exceeding the transcranial motor threshold at increasing stimulation intensities. A ring block around the vertex is advised to reduce interference by extracranial mMEPs. mMEPs reflect the functional integrity of the route along the brainstem nuclei, extrapyramidal motor tracts, propriospinal neurons, and motoneurons. The corticospinal tract appears subordinate in horses. TMS and TES are interchangeable for assessing the functional integrity of motor functions of the spinal cord. However, TES reveals significantly shorter MLTs, higher conduction velocities, and better reproducibility.

Auditory Brainstem Responses in Children with Auditory Processing Disorder

The ASHA recommends including electrophysiological measures in an auditory processing disorder (APD) assessment battery, but few audiologists do so, potentially because of limited published evidence for its utility. This study compared the auditory brainstem responses (ABRs) of children with APD with age-matched children and adults. This study retrospectively examined the records of 108 children suspected of APD (sAPD) who had click-evoked ABRs recorded as part of their clinical assessment. Twenty adults and 22 typically developing (TD) children were recruited as controls. Click-evoked ABRs were recorded at slow (13.3 clicks/sec) and faster (57.7 clicks/sec) stimulation rates. ABRs were analyzed using typical clinical measures (latencies and interpeak intervals for waves I, III, and V) and using a model proposed by Ponton et al that offered a more detailed analysis of axonal conduction time and synaptic transmission delay. Both clinical measures and the Ponton model analysis showed no significant differences between TD children and adults. Children sAPD showed absolute latencies that were significantly prolonged when compared with adults but not when compared with TD children. But individual children sAPD showed clinically significant delays (>2 standard deviations of TD children's data). Examination of responses delineating axonal versus synaptic transmission showed significant delays in synaptic transmission in the group of children sAPD in comparison to TD children and adults. These results suggest that a significant portion of children with listening difficulties showed evidence of reduced or atypical brainstem functioning. Examining the responses for axonal and synaptic delays revealed evidence of a synaptic pattern of abnormalities in a significant portion (37.03%) of children sAPD. Such observations could provide objective evidence of factors potentially contributing to listening difficulties that are frequently reported in children identified with APD. Children sAPD often showed abnormalities in the ABR, suggesting a neurophysiologic origin of their reported difficulties, frequently originating at or before the first synapse. This study provides supportive evidence for the value of click-evoked ABRs in comprehensive auditory processing assessment batteries.

Locus Coeruleus Optogenetic Light Activation Induces Long-Term Potentiation of Perforant Path Population Spike Amplitude in Rat Dentate Gyrus.

Norepinephrine (NE) in dentate gyrus (DG) produces NE-dependent long-term potentiation (NE-LTP) of the perforant path-evoked potential population spike both in vitro and in vivo. Chemical activators infused near locus coeruleus (LC), the source of DG NE, produce a NE-LTP that is associative, i.e., requires concurrent pairing with perforant path (PP) input. Here, we ask if LC optogenetic stimulation that allows us to activate only LC neurons can induce NE-LTP in DG. We use an adeno-associated viral vector containing a depolarizing channel (AAV8-Ef1a-DIO-eChR2(h134r)-EYFP-WPRE) infused stereotaxically into the LC of TH:Cre rats to produce light-sensitive LC neurons. A co-localization of ~62% in LC neurons was observed for these channels. Under urethane anesthesia, we demonstrated that 5–10 s 10 Hz trains of 30 ms light pulses in LC reliably activated neurons near an LC optoprobe. Ten minutes of the same train paired with 0.1 Hz PP electrical stimulation produced a delayed NE-LTP of population spike amplitude, but not EPSP slope. A leftward shift in the population spike input/output curve at the end of the experiment was also consistent with long-term population spike potentiation. LC neuron activity during the 10 min light train was unexpectedly transient. Increased LC neuronal firing was seen only for the first 2 min of the light train. NE-LTP was more delayed and less robust than reported with LC chemo-activation. Previous estimates of LC axonal conduction times suggest acute release of NE occurs 40–70 ms after an LC neuron action potential. We used single LC light pulses to examine acute effects of NE release and found potentiated population spike amplitude when a light pulse in LC occurred 40–50 ms, but not 20–30 ms, prior to a PP pulse, consistent with conduction estimates. These effects of LC optogenetic activation reinforce evidence for a continuum of NE potentiation effects in DG. The single pulse effects mirror an earlier report using LC electrical stimulation. These acute effects support an attentional role of LC activation. The LTP of PP responses induced by optogenetic LC activation is consistent with the role of LC in long-term learning and memory.

Axonal Conduction Delays, Brain State, and Corticogeniculate Communication.

Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40-50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times.SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40-50 ms. Here, in the corticogeniculate visual system of awake rabbits, we investigate the functional significance of this axonal diversity, and the effects of shifting alert/nonalert brain states on corticogeniculate processing. We show that axonal conduction times are strongly related to multiple visual response properties, suggesting a continuum of visual responsiveness spanning the spectrum of corticogeniculate axonal conduction times. We also show that transitions between awake brain states powerfully affect corticogeniculate processing, in some ways more strongly than in layer 4.

Input timing for spatial processing is precisely tuned via constant synaptic delays and myelination patterns in the auditory brainstem.

Precise timing of synaptic inputs is a fundamental principle of neural circuit processing. The temporal precision of postsynaptic input integration is known to vary with the computational requirements of a circuit, yet how the timing of action potentials is tuned presynaptically to match these processing demands is not well understood. In particular, action potential timing is shaped by the axonal conduction velocity and the duration of synaptic transmission delays within a pathway. However, it is not known to what extent these factors are adapted to the functional constraints of the respective circuit. Here, we report the finding of activity-invariant synaptic transmission delays as a functional adaptation for input timing adjustment in a brainstem sound localization circuit. We compared axonal and synaptic properties of the same pathway between two species with dissimilar timing requirements (gerbil and mouse): In gerbils (like humans), neuronal processing of sound source location requires exceptionally high input precision in the range of microseconds, but not in mice. Activity-invariant synaptic transmission and conduction delays were present exclusively in fast conducting axons of gerbils that also exhibited unusual structural adaptations in axon myelination for increased conduction velocity. In contrast, synaptic transmission delays in mice varied depending on activity levels, and axonal myelination and conduction velocity exhibited no adaptations. Thus, the specializations in gerbils and their absence in mice suggest an optimization of axonal and synaptic properties to the specific demands of sound localization. These findings significantly advance our understanding of structural and functional adaptations for circuit processing.

The Effect of Sleep on the Fast and Slow Components of the Auditory Brainstem Response: A Case Study

This study examined the effects of sleep on the slow and fast components of the auditory brainstem response (ABR) in a human subject. ABR waveforms, electroencephalogram and rectal temperature were recorded from 1 adult male during overnight sleep, and the slow and fast components of the ABR were extracted using a six-level over-complete discrete wavelet transform (OCDWT). Initial results suggested ABR wave V, and its corresponding slow and fast components, increased in latency during sleep stages 2 and 4 relative to the awake state, but autoregressive integrated moving average (ARIMA) time series analyses showed these increases were best explained by decreases in body temperature. These results support suggestions that decreases in body temperature during sleep result in an increase in both synaptic transmission and axonal conduction times in the 8th cranial nerve and auditory brainstem, and that these changes are reversible.

Is a cortical spike discharge "transferred" to the contralateral cortex via the corpus callosum?: An intraoperative observation of electrocorticogram and callosal compound action potentials.

By means of the intraoperative electrophysiologic observation, we reevaluated the "transfer" theory that a transcallosal volley invoked by a cortical spike discharge in one hemisphere directly causes its contralateral counterpart via the corpus callosum (CC). Twenty-six patients who underwent corpus callosotomy were the subjects of this study. Intraoperatively, electrocorticograms from both hemispheres were simultaneously monitored with callosal compound action potentials (CCAPs) from the CC. Analysis was conducted on (a) the interhemispheric delay of bilaterally synchronous spike-and-wave discharges (BSSWs), and (b) the chronological relation between BSSWs and CCAPs. The side of prior spike discharges was never fixed but was occasionally reversed. Interhemispheric delays between the BSSWs were not constant, regardless of direction, and fluctuated in all patients. Most of the interhemispheric delays were distributed within 20 ms with a mode of 0 ms. The waveform of the CCAP was characterized by slow-rising negative potential change that attained its peak after a cortical spike discharge. These findings were identical in all the patients regardless of whether the BSSWs were changed or unchanged after callosotomy. If the "transfer" role of the CC is true, interhemispheric delays between BSSWs must be longer than interhemispheric axonal conduction time (about 20 ms), and a preceding cortical spike discharge must produce a CCAP and then a contralateral one in order of time. However, this hypothesis was not confirmed in the present study. We propose the interhemispheric recruitment of the epileptogenic state as a different role of the CC on epileptogenesis.

The role of timing in the brain stem auditory nuclei of vertebrates.

Vertebrate animals gain biologically important information from environmental sounds. Localization of sound sources enables animals to detect and respond appropriately to danger, and it allows predators to detect and localize prey. In many species, rapidly fluctuating sounds are also the basis of communication between conspecifics. This information is not provided directly by the output of the ear but requires processing of the temporal pattern of firing in the tonotopic array of auditory nerve fibers. The auditory nerve feeds information through several parallel ascending pathways. Anatomical and electrophysiological specializations for conveying precise timing, including calyceal synaptic terminals and matching axonal conduction times, are evident in several of the major ascending auditory pathways through the ventral cochlear nucleus and its nonmammalian homologues. One pathway that is shared by all higher vertebrates makes an ongoing comparison of interaural phase for the localization of sound in the azimuth. Another pathway is specifically associated with higher frequency hearing in mammals and is thought to make use of interaural intensity differences for localizing high-frequency sounds. Balancing excitation from one ear with inhibition from the other in rapidly fluctuating signals requires that the timing of these synaptic inputs be matched and constant for widely varying sound stimuli in this pathway. The monaural nuclei of the lateral lemniscus, whose roles are not understood (although they are ubiquitous in higher vertebrates), receive input from multiple pathways that encode timing with precision, some through calyceal endings.

Motoneuron plasticity underlying operantly conditioned decrease in primate H-reflex.

1. Monkeys can gradually increase or decrease the size of the triceps surae H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To determine the location and nature of the spinal cord plasticity and define its role in the behavioral change (i.e., H-reflex increase or decrease) we have recorded intracellularly from triceps surae motoneurons in conditioned animals and compared the results with data from naive (i.e., unconditioned) animals. 2. Eleven monkeys (Macaca nemestrina, male) were exposed to the HRdown conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was below a criterion value. In six animals (5.1-8.2 kg) H-reflex size in the trained leg fell to 24-58% of its initial value, whereas in the other five animals (4.0-5.5 kg) it remained at 92-114% of its initial value. This outcome, which was in accord with recent data indicating that success in HRdown conditioning is age dependent, allowed comparison of intracellular data from successful HRdown animals with data from unsuccessful animals as well as with data from naive (i.e., unconditioned) animals. 3. Intracellular recordings were obtained from 221 triceps surae motoneurons on trained and control sides of successful and unsuccessful HRdown animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potentials to peripheral nerve stimulation. Results were compared with data from 109 triceps surae motoneurons in naive animals. 4. Motoneurons from the trained side of successful HRdown animals had a significantly more positive average firing threshold (-52 vs. -55 mV) and a significantly lower average conduction velocity (67 vs. 71 m/s) than those from naive animals. In contrast, motoneurons from the trained side of unsuccessful HRdown animals were not significantly different from naive motoneurons. 5. These data are consistent with the hypothesis that operantly conditioned decrease in H-reflex size is due to a positive shift in motoneuron firing threshold and a consequent increase in the depolarization needed to reach that threshold. 6. The more positive firing threshold, if present in the axon as well as in the soma, could also account for the decreased conduction velocity observed in motoneurons from the trained side of successful animals.

The relationship between axonal and perisynaptic conduction times in the retinogeniculate pathway of cats

We examined the degree to which conduction velocity differences between X- and Y-cells are preserved during transmission through the retinogeniculate synaptic zone. This analysis focused upon two measures: (1) axon time; and (2)_perisynaptic time. The first is the time required for an action potential to travel from the optic chiasm to the point of major branching in the optic tract. The second is the sum of terminal invasion time, synaptic delay, and the time required for postsynaptic processes which precede the generation of an action potential. The X- and Y-cell distributions of axonal conduction times differed markedly. In contrast, the X- and Y- distributions of perisynaptic conduction times overlapped extensively. Therefore, the overlap in optic chiasm latency distributions between geniculate X- and Y-cells arises primarily from the perisynaptic zone. Further, on a unit-by-unit basis, we observed small but significant negative correlations between axon conduction times and perisynaptic times within both the X- and Y-cell classes. That is, units innervated by faster conducting afferents tended to have longer perisynaptic processing times, and vice versa. This sort of relationship may act to enhance within-class synchrony in postsynaptic activity.

Relationship among recruitment order, axonal conduction velocity, and muscle-unit properties of type-identified motor units in cat plantaris muscle

A strict interpretation of the size-principle hypothesis (37, 39-41) is that a muscle's motor units should be recruited in an ascending order according to both the size of their motoneurons and the size of their innervated muscle units (for reviews see Refs. 9, 39, 73). Studies of large mixed muscles in the cat hindlimb, however, have shown that motor axonal conduction velocity and tetanic tension, which are frequently considered indices of motoneuron and muscle-unit size, respectively, are uncorrelated in the fast-twitch (type F) motor-unit subpopulation (12, 13, 23, 24, 30, 32, 63, 71, 79). Attempting to focus on type F units, we compared the recruitment order of 42 pairs of cat plantaris (PL) motor units with both axonal conduction velocity and tetanic tension as well as with other muscle-unit properties. Single PL alpha-motor axons were functionally isolated in intact L7 ventral root filaments of decerebrate cats. Tension responses produced by stimulating each isolated motor axon were used to find the tetanic tension of the muscle unit and to classify the unit (12) as either type S (slow twitch, fatigue resistant), type FR (fast twitch, fatigue resistant), type FI (fast twitch, intermediate fatigability), or type FF (fast twitch, highly fatigable). Conduction velocity of each isolated axon was computed from measurements of axonal conduction time and length. The axon's reflex discharges were recorded from the proximal end of the cut filament and compared with the discharges of another PL axon residing in a different, previously cut filament of the same cat. The recruitment order of each motor-unit pair studied was found during reflexes elicited by homonymous muscle stretch, tendon taps, or single shocks at group I intensity to the PL nerve. If either axon of the pair failed to discharge, as often was the case with the high-threshold type F units, the monosynaptic reflex was facilitated by a 500-pps conditioning train applied proximal to a complete reversible cooling block of the PL nerve. In all 42 pairs studied, the weaker motor unit had the lower functional threshold for recruitment. Recruitment also invariably followed the order S greater than FR greater than FI greater than FF units. The motor unit of a pair with the higher resistance to fatigue thus always had the lower functional threshold. In 21 of the 22 pairs containing at least one type S motor unit, the unit with the slower-conducting motor axon had the lower functional threshold for recruitment.(ABSTRACT TRUNCATED AT 400 WORDS)

Auditory brainstem responses during systemic infusion of lidocaine.

Auditory brainstem-evoked responses (ABR) to clicks were recorded in unanesthetized restrained cats before, during, and after systemic intravenous infusion of lidocaine hydrochloride. The drug was infused continuously at varying rates. Lidocaine's major effect on ABR was to lengthen latent periods to all wave-form peaks in proportion with the infusion rate. The effect on latent periods was cumulative throughout the auditory brainstem, ie, all interpeak time intervals increased. Increases in ABR latencies were not due to reductions in effective stimulus intensity because lidocaine did not reduce ABR component amplitudes or increase thresholds. The effects of the drug were reversible. The data are consistent with the notion that lidocaine, directly or indirectly, works throughout the auditory brainstem to increase axonal and synaptic conduction times.