Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. II. Cortical neurons excited by somatic stimuli

1. Of the sample of 322 neurons located in somatosensory cortex and tested for their responsiveness to somatic stimulation, 91 (28%) responded to stimuli applied to the skin. The majority were located in the middle cortical layers. Each of the cells subjected to tests with glutamate and acetylcholine (ACh) was rapidly adapting to cutaneous stimuli, giving a response at the onset of skin indentation and sometimes after the stimulus withdrawal. 2. Of the 30 cells tested by pairing basal forebrain (BF) stimulation with cutaneous stimulation. 18 (60%) displayed enhanced responses to the same cutaneous stimulus after the pairing. These effects lasted for greater than 5 min in 17 cases, persisting for as long as the cell was studied, sometimes greater than 1 h. 3. The enhanced responsiveness to cutaneous stimuli could not be reversed by atropine, but in each of the 11 cells where atropine was administered while the BF stimulus was paired with the skin stimulus, the pairing produced no enhancement. 4. We conclude that pairing a BF stimulus with a cutaneous stimulus leads to long-term facilitation of the responsiveness of the cortical neuron subjected to this treatment and that this effect is mediated by the release of acetylcholine from BF cholinergic neurons that act on muscarinic receptors found on neurons in the somatosensory cortex.     

The pedunculopontine tegmental nucleus: a second cholinergic source for frequency-specific auditory plasticity

Cholinergic modulation is essential for many brain functions and is an indispensable component of the prevalent models attempting to understand the neural mechanism responsible for learning-induced auditory plasticity. Unlike the cholinergic basal forebrain, the cholinergic pedunculopontine tegmental nucleus (PPTg) has received little attention. This study was designed to confirm whether the PPTg enables frequency-specific plasticity in the ventral division of the medial geniculate body of the thalamus (MGBv). Using the mouse model, we paired electrical stimulation of the PPTg with tone stimulation to help define the role of the PPTg. The receptive fields of MGBv neurons were examined before and after the paired stimulation; they were quantified in this study by best frequency (BF), response threshold, dynamic range, and spike number. We found that the electrical stimulation of the PPTg together with a tone presentation shifted the BFs of MGBv neurons upward when the frequency of the paired tone was higher than that of the control BF. Similarly, the BFs shifted downward when the frequency of the paired tone was lower than that of the control BF. The BFs of MGBv neurons, however, remained unchanged when the frequency of the paired tone was the same as that of the control BF. There was a linear relationship between the BF shift of MGBv neurons and the difference between the frequency of the paired tone and the control BF of MGBv neurons. Highly frequency specific changes were also observed in the response threshold, dynamic range, and spike number. This frequency-specific plasticity was largely eliminated by the microinjection of the muscarinic receptor antagonist atropine into the MGBv before the paired stimulation. Our findings suggest that the PPTg, like the cholinergic basal forebrain, is an important cholinergic source that enables frequency-specific plasticity in the central auditory system.     

Basal forebrain stimulation induces discriminative receptive field plasticity in the auditory cortex.

Learning alters receptive field (RF) tuning in the primary auditory cortex (ACx) to emphasize the frequency of a tonal conditioned stimulus. RF plasticity is a candidate substrate of memory, as it is associative, specific, discriminative, rapidly induced, and enduring. The authors hypothesized that it is produced by the release of acetylcholine in the ACx from the basal forebrain (BasF), caused by presentation of reinforced but not nonreinforced conditioned stimuli. Waking adult male Hartley guinea pigs (n = 16) received 1 of 2 tones followed by BasF stimulation, in a single session of 30 pseudo-random order trials each. RFs from neuronal discharges before and after differential pairing revealed the induction of predicted plasticity, as well as increased responses to the paired tone and decreased responses to the unpaired tone. Thus, highly specific, learning-induced RF plasticity in the ACx may be produced by activation of the BasF by a reinforced conditioned stimulus.     

Plasticity in the rat posterior auditory field following nucleus basalis stimulation

Classical conditioning paradigms have been shown to cause frequency-specific plasticity in both primary and secondary cortical areas. Previous research demonstrated that repeated pairing of nucleus basalis (NB) stimulation with a tone results in plasticity in primary auditory cortex (A1), mimicking the changes observed after classical conditioning. However, few studies have documented the effects of similar paradigms in secondary cortical areas. The purpose of this study was to quantify plasticity in the posterior auditory field (PAF) of the rat after NB stimulation paired with a high-frequency tone. NB-tone pairing increased the frequency selectivity of PAF sites activated by the paired tone. This frequency-specific receptive field size narrowing led to a reorganization of PAF such that responses to low- and mid-frequency tones were reduced by 40%. Plasticity in A1 was consistent with previous studies -- pairing a high-frequency tone with NB stimulation expanded the high-frequency region of the frequency map. Receptive field sizes did not change, but characteristic frequencies in A1 were shifted after NB-tone pairing. These results demonstrate that experience-dependent plasticity can take different forms in both A1 and secondary auditory cortex.     

Acetylcholine-dependent induction and expression of functional plasticity in the barrel cortex of the adult rat.

The involvement of acetylcholine (ACh) in the induction of neuronal sensory plasticity is well documented. Recently we demonstrated in the somatosensory cortex of the anesthetized rat that ACh is also involved in the expression of neuronal plasticity. Pairing stimulation of the principal whisker at a fixed temporal frequency with ACh iontophoresis induced potentiations of response that required re-application of ACh to be expressed. Here we fully characterize this phenomenon and extend it to stimulation of adjacent whiskers. We show that these ACh-dependent potentiations are cumulative and reversible. When several sensori-cholinergic pairings were applied consecutively with stimulation of the principal whisker, the response at the paired frequency was further increased, demonstrating a cumulative process that could reach saturation levels. The potentiations were specific to the stimulus frequency: if the successive pairings were done at different frequencies, then the potentiation caused by the first pairing was depotentiated, whereas the response to the newly paired frequency was potentiated. During testing, the potentiation of response did not develop immediately on the presentation of the paired frequency during application of ACh: the analysis of the kinetics of the effect indicates that this process requires the sequential presentation of several trains of stimulation at the paired frequency to be expressed. We present evidence that a plasticity with similar characteristics can be induced for responses to stimulation of an adjacent whisker, suggesting that this potentiation could participate in receptive field spatial reorganizations. The spatial and temporal properties of the ACh-dependent plasticity presented here impose specific constraints on the underlying cellular and molecular mechanisms.     

Background sounds contribute to spectrotemporal plasticity in primary auditory cortex

The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8–4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity     

Selective potentiation of crossed vs. uncrossed inputs from lateral geniculate nucleus to visual cortex by the basal forebrain: Potential facilitation of rodent binocularity

Cholinergic projections originating in the basal forebrain (BF) play important roles in the heterosynaptic facilitation of synaptic strength in various sensory cortices, including the primary visual cortex (V1). Here, using urethane-anesthetized rats, we find that pairing burst stimulation of the BF with single pulse stimulation of the lateral geniculate nucleus (LGN) does not consistently increase field postsynaptic potentials (fPSPs) in V1 elicited by ipsilateral LGN stimulation. However, longer latency fPSPs recorded in V1 in response to stimulation of the contralateral LGN, reflecting crossed, polysynaptic inputs, show significant potentiation when paired with preceding BF stimulation. This synaptic enhancement requires relatively short time intervals between paired BF burst and LGN pulse stimulation (40 ms) and is abolished by systemic or local V1 muscarinic receptor blockade (scopolamine), while systemic nicotinic receptor blockade (mecamylamine) is ineffective. Together, these data provide evidence for a differential capacity for cholinergic/muscarinic-dependent plasticity induction among different signals in V1, with inputs reaching V1 from the contralateral LGN exhibiting potentiation in the face of stable strength in ipsilateral LGN-V1 projections. This preferential readiness for potentiation in crossed fiber systems could serve to amplify binocular responses in V1 elicited by synchronized excitation of ipsi- and contralateral LGN neurons.     

Electrophysiological evidence for the existence of a posterior cortical-prefrontal-basal forebrain circuitry in modulating sensory responses in visual and somatosensory rat cortical areas

The prefrontal cortex (PFC) receives input from sensory neocortical regions and sends projections to the basal forebrain (BF). The present study tested the possibility that pathways from sensory cortical regions via the PFC-BF and from the BF back to specific sensory cortical areas could modulate sensory responses. Two prefrontal areas that responded to stimulation of the primary somatosensory and visual cortices were delineated: an area encompassing the rostral part of the cingulate cortex that responded to visual cortex stimulation, and a region dorso-lateral to the first in the precentral-motor association area that reacted to somatosensory cortex stimulation. Moreover, BF neurons responded to PFC electrical stimulation. They were located in the ventral pallidum, substantia innominata and the horizontal limb of the diagonal-band areas. Of the responsive BF neurons 42% reacted only to stimulation of 'visually-responsive,' 33% responded only to the 'somatosensory-responsive' prefrontal sites and the remaining neurons reacted to both prefrontal cortical areas. The effect of BF and PFC stimulations on somatosensory and visual-evoked potentials was tested. BF stimulation increased the amplitude of both sensory-evoked potentials. However, stimulation of the 'somatosensory-responsive' prefrontal area increased only somatosensory-evoked potentials while 'visually-responsive' prefrontal-area stimulation increased only visual-evoked potentials. Atropine blocked both facilitatory effects.The proposed cortico-prefronto-basalo-cortical circuitry may have an important role in cortical plasticity and selective attention.     

Plasticity of temporal information processing in the primary auditory cortex

Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone sequences faster than 12 pulses per second (pps). To test whether experience can modify this maximum following rate in adult rats, trains of brief tones with random carrier frequency but fixed repetition rate were paired with electrical stimulation of the nucleus basalis (NB) 300 to 400 times per day for 20-25 days. Pairing NB stimulation with 5-pps stimuli markedly decreased the cortical response to rapidly presented stimuli, whereas pairing with 15-pps stimuli significantly increased the maximum cortical following rate. In contrast, pairing with fixed carrier frequency 15-pps trains did not significantly increase the mean maximum following rate. Thus this protocol elicits extensive cortical remodeling of temporal response properties and demonstrates that simple differences in spectral and temporal features of the sensory input can drive very different cortical reorganizations.     

Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex

We investigated the relationships between cortical arousal and cholinergic facilitation of evoked responses in the auditory cortex. The basal forebrain (BF) was stimulated unilaterally, while cluster recordings were obtained simultaneously from both auditory cortices in urethane-anesthetized rats. The global electroencephalogram (EEG; large frontoparietal derivation) and the local EEG (from the auditory cortex) were recorded. The BF was stimulated at two intensities, a lower one which did not desynchronize the EEG and a higher one which did. Twenty pairing trials were delivered, during which a tone was presented 50 ms after the end of the BF stimulation. At low intensity, the pairing procedure led to a transient increase in the ipsilateral tone-evoked responses. At high intensity, the pairing increased the ipsilateral evoked responses up to 15 min after pairing. Such effects were not observed for the contralateral recordings. Systemic atropine injection prevented the facilitations observed ipsilaterally. BF stimulations alone did not induce any increased evoked response either at low or at high intensity. These results show (1) that a tone, presented while the cortex is activated by cholinergic neurons of the BF, evokes enhanced cortical responses, and (2) that the duration of this facilitation is dependent on the stimulation intensity. These results are discussed in the context of neural mechanisms involved in general arousal and cortical plasticity.     

Learning-Induced Receptive Field Plasticity in the Primary Auditory Cortex

Primary sensory cortex in the adult is modified by learning. The primary auditory cortex is retuned when a tone is paired with a behaviorally relevant reinforcer. Frequency receptive fields are shifted toward or to the frequency of the signal stimulus, yielding enhanced processing and representation of important frequencies. Receptive field plasticity constitutes “physiological memory” because, like much memory, it is associative, highly specific, rapidly-induced, and retained indefinitely, at least for months. The basal forebrain cholinergic system may be a substrate because its paired activation is sufficient to induce receptive field plasticity in the absence of actual behavioral learning experiences.     

Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. I. Cortical neurons excited by glutamate

1. Microelectrodes attached to iontophoretic pipettes were used to isolate 410 single neurons in the primary somatosensory cortex of halothane-anesthetized cats. Basal forebrain (BF) stimulation, when paired with pulses of iontophoretically administered glutamate, affected the responsiveness in 24 (54%) of 39 neurons; 17 were facilitated, and seven were inhibited. Five minutes after BF stimulation the average response for a sample of 20 cells was enhanced by 45% (+/- 19). All but one of the effects lasted as long as the cell was studied, often greater than 1 h. 2. When atropine was administered while the BF was stimulated during glutamate excitation, 7 of 16 cells were enhanced, but the average increase was only 16% (+/- 15) for a sample of 15 cells. After the atropine had dissipated, four cells were enhanced by the BF stimulus. In three of these the enhancement had been blocked previously by atropine. 3. BF stimulation had effects similar to iontophoretically administered acetylcholine (ACh), but the effects appeared more frequently with BF stimulation than they had with acetylcholine administration. 4. We propose that the enhanced neuronal responsiveness is due to the release of acetylcholine by cortical terminals of cholinergic neurons located in the BF. The BF stimulus may be more effective than acetylcholine administration because corticopetal cholinergic fibers may end in the immediate vicinity of receptors responsible for long-term changes in membrane permeability.     

Long-term enhancement of evoked potentials in cat somatosensory cortex produced by co-activation of the basal forebrain and cutaneous receptors

Summary Averaged evoked potentials from primary somatosensory cortex (SEPs) were recorded before and after pairing the peripheral stimuli with electrical activation of the basal forebrain (BF) in anesthetized cats. Four pulses at 400 Hz were delivered to the BF 120 ms before each cutaneous stimulus and 10 to 660 such pairings were found to produce an enlargement of the SEP in 10 of 11 animals. The average increase in amplitude of the initial peak of the SEP was 69%. The SEP remained enhanced in five of six animals that were tested an hour or more after the pairing, and in one case the SEP was tested 4.5 h after pairing without diminution. The effective BF sites were located in the substantia innominata and at the rostral pole of the globus pallidus, regions known to contain many cholinergic cell bodies. Enhancement occurred consistently only if stimulation of the BF site elicited a positive wave in the cortex at a latency of 11 to 18 ms. Repeated BF stimulation without cutaneous input did not produce a change in subsequent SEPs. The long-term changes described here may be involved in experimentally- and naturally-induced cortical reorganization.     

Position-specific adaptation in simple cell receptive fields of the cat striate cortex.

1. Responses of simple cells in cat striate cortex were studied with flashed light-slit stimuli. The responses to bars flashed in different positions in the receptive field were assessed quantitatively before and after periods of prolonged stimulation of one small region. This type of prolonged stimulation resulted in reduced responsivity over a limited zone within the simple cell receptive field. 2. The adaptation-induced responsivity decrement was generally confined to the receptive-field subregion that was adapted (either ON or OFF). Prolonged stimulation within an ON region did not usually result in adaptation effects that spread into neighboring OFF regions. Furthermore, the adaptation-induced response decrement did not necessarily spread throughout the subregion in which the adapting stimulus was presented. The adaptation effects from prolonged stimulation at a single receptive-field position spread throughout the subregion in nearly one-half of the 25 cells examined for position-specific adaptation. Another subpopulation of neurons (n = 12) displayed adaptation effects that spread through only one-half of the subregion, whereas in two neurons the spread of the adaptation effect was even more restricted and encompassed only one-fourth of the subregion. 3. The spread of adaptation was not systematically related to the size of the stimulus presented, the size of the receptive field, or the magnitude of the adaptation-induced response decrements but was significantly correlated with the spatial wavelength of the cell (the reciprocal of the cell's preferred spatial frequency) and with the size of the subregion in which the adapting stimulus was presented. Cells with large receptive-field subregions and long wave-lengths showed adaptation effects that spread further than those of cells with small subregions. 4. The adaptation effects from repeated stimulation at a single receptive-field position did not spread symmetrically across the receptive field, and the preferred direction of motion for a given cell indicated the direction of the asymmetric spread of the adaptation. Receptive-field positions that would be stimulated by a light slit originating at the point of adaptation and moving in the preferred direction (preferred side) showed greater adaptation-induced response decrements than did receptive-field positions that would be stimulated by a light slit moving in the opposite direction from the point of adaptation (nonpreferred side). There was significant enhancement of responses at some receptive-field positions on the nonpreferred side of the point of adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Corticogeniculate neurons, corticotectal neurons, and suspected interneurons in visual cortex of awake rabbits: receptive-field properties, axonal properties, and effects of EEG arousal

The intrinsic stability of the rabbit eye was exploited to enable receptive-field analysis of antidromically identified corticotectal (CT) neurons (n = 101) and corticogeniculate (CG) neurons (n = 124) in visual area I of awake rabbits. Eye position was monitored to within 1/5 degrees. We also studied the receptive-field properties of neurons synaptically activated via electrical stimulation of the dorsal lateral geniculate nucleus (LGNd). Whereas most CT neurons had either complex (59%) or motion/uniform (15%) receptive fields, we also found CT neurons with simple (9%) and concentric (4%) receptive fields. Most complex CT cells were broadly tuned to both stimulus orientation and velocity, but only 41% of these cells were directionally selective. We could elicit no visual responses from 6% of CT cells, and these cells had significantly lower conduction velocities than visually responsive CT cells. The median spontaneous firing rates for all classes of CT neurons were 4-8 spikes/s. CG neurons had primarily simple (60%) and concentric (9%) receptive fields, and none of these cells had complex receptive fields. CG simple cells were more narrowly tuned to both stimulus orientation and velocity than were complex CT cells, and most (85%) were directionally selective. Axonal conduction velocities of CG neurons (mean = 1.2 m/s) were much lower than those of CT neurons (mean = 6.4 m/s), and CG neurons that were visually unresponsive (23%) had lower axonal conduction velocities than did visually responsive CG neurons. Some visually unresponsive CG neurons (14%) responded with saccadic eye movements. The median spontaneous firing rates for all classes of CG neurons were less than 1 spike/s. All neurons synaptically activated via LGNd stimulation at latencies of less than 2.0 ms had receptive fields that were not orientation selective (89% motion/uniform, 11% concentric), whereas most cells with orientation-selective receptive fields had considerably longer synaptic latencies. Most short-latency motion/uniform neurons responded to electrical stimulation of the LGNd (and visual area II) with a high-frequency burst (500-900 Hz) of three or more spikes. Action potentials of these neurons were of short duration, thresholds of synaptic activation were low, and spontaneous firing rates were the highest seen in rabbit visual cortex. These properties are similar to those reported for interneurons in several regions in mammalian central nervous system. Nonvisual sensory stimuli that resulted in electroencephalographic arousal (hippocampal theta activity) had a profound effect on the visual responses of many visual cortical neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of primate SI cortical neurons to noxious stimuli

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.     

Plasticity of bat's central auditory system evoked by focal electric stimulation of auditory and/or somatosensory cortices

Recent findings indicate that the corticofugal system would play an important role in cortical plasticity as well as collicular plasticity. To understand the role of the corticofugal system in plasticity, therefore, we studied the amount and the time course of plasticity in the inferior colliculus (IC) and auditory cortex (AC) evoked by focal electrical stimulation of the AC and also the effect of electrical stimulation of the somatosensory cortex on the plasticity evoked by the stimulation of the AC. In adult big brown bats (Eptesicus fuscus), we made the following major findings. 1) Electric stimulation of the AC evokes best frequency (BF) shifts, i.e., shifts in frequency-response curves of collicular and cortical neurons. These BF shifts start to occur within 2 min, reach a maximum (or plateau) at 30 min, and then recover approximately 180 min after a 30-min-long stimulus session. When the stimulus session is lengthened from 30 to 90 min, the plateau lasts approximately 60 min, but BF shifts recover approximately 180 min after the session. 2) The electric stimulation of the somatosensory cortex delivered immediately after that of the AC, as in fear conditioning, evokes a dramatic lengthening of the recovery period of the cortical BF shifts but not that of the collicular BF shift. The electric stimulation of the somatosensory cortex delivered before that of the AC, as in backward conditioning, has no effect on the collicular and cortical BF shifts. 3) Electric stimulation of the AC evokes BF shifts not only in the ipsilateral IC and AC but also in the contralateral IC and AC. BF shifts are smaller in amount and shorter in recovery time for contralateral collicular and cortical neurons than for ipsilateral ones. Our findings support the hypothesis that the AC and the corticofugal system have an intrinsic mechanism for reorganization of the IC and AC, that the reorganization is highly specific to a value of an acoustic parameter (frequency), and that the reorganization is augmented by excitation of nonauditory sensory cortex that makes the acoustic stimulus behaviorally relevant to the animal through associative learning.     

Temporal plasticity in the primary auditory cortex induced by operant perceptual learning

Processing of rapidly successive acoustic stimuli can be markedly improved by sensory training. To investigate the cortical mechanisms underlying such temporal plasticity, we trained rats in a 'sound maze' in which navigation using only auditory cues led to a target location paired with food reward. In this task, the repetition rate of noise pulses increased as the distance between the rat and target location decreased. After training in the sound maze, neurons in the primary auditory cortex (A1) showed greater responses to high-rate noise pulses and stronger phase-locking of responses to the stimuli; they also showed shorter post-stimulation suppression and stronger rebound activation. These improved temporal dynamics transferred to trains of pure-tone pips. Control animals that received identical sound stimulation but were given free access to food showed the same results as naive rats. We conclude that this auditory perceptual learning results in improvements in temporal processing, which may be mediated by enhanced cortical response dynamics.     

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10–25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50–60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.     

Facilitatory and inhibitory frequency tuning of combination-sensitive neurons in the primary auditory cortex of mustached bats

Mustached bats, Pteronotus parnellii parnellii, emit echolocation pulses that consist of four harmonics with a fundamental consisting of a constant frequency (CF(1-4)) component followed by a short, frequency-modulated (FM(1-4)) component. During flight, the pulse fundamental frequency is systematically lowered by an amount proportional to the velocity of the bat relative to the background so that the Doppler-shifted echo CF(2) is maintained within a narrowband centered at approximately 61 kHz. In the primary auditory cortex, there is an expanded representation of 60.6- to 63. 0-kHz frequencies in the "Doppler-shifted CF processing" (DSCF) area where neurons show sharp, level-tolerant frequency tuning. More than 80% of DSCF neurons are facilitated by specific frequency combinations of approximately 25 kHz (BF(low)) and approximately 61 kHz (BF(high)). To examine the role of these neurons for fine frequency discrimination during echolocation, we measured the basic response parameters for facilitation to synthesized echolocation signals varied in frequency, intensity, and in their temporal structure. Excitatory response areas were determined by presenting single CF tones, facilitative curves were obtained by presenting paired CF tones. All neurons showing facilitation exhibit at least two facilitative response areas, one of broad spectral tuning to frequencies centered at BF(low) corresponding to a frequency in the lower half of the echolocation pulse FM(1) sweep and another of sharp tuning to frequencies centered at BF(high) corresponding to the CF(2) in the echo. Facilitative response areas for BF(high) are broadened by approximately 0.38 kHz at both the best amplitude and 50 dB above threshold response and show lower thresholds compared with the single-tone excitatory BF(high) response areas. An increase in the sensitivity of DSCF neurons would lead to target detection from farther away and/or for smaller targets than previously estimated on the basis of single-tone responses to BF(high). About 15% of DSCF neurons show oblique excitatory and facilitatory response areas at BF(high) so that the center frequency of the frequency-response function at any amplitude decreases with increasing stimulus amplitudes. DSCF neurons also have inhibitory response areas that either skirt or overlap both the excitatory and facilitatory response areas for BF(high) and sometimes for BF(low). Inhibition by a broad range of frequencies contributes to the observed sharpness of frequency tuning in these neurons. Recordings from orthogonal penetrations show that the best frequencies for facilitation as well as excitation do not change within a cortical column. There does not appear to be any systematic representation of facilitation ratios across the cortical surface of the DSCF area.