Multiunit Spiking Activity Research Articles

Optimizing the Decoding of Movement Goals from Local Field Potentials in Macaque Cortex

The successful development of motor neuroprosthetic devices hinges on the ability to accurately and reliably decode signals from the brain. Motor neuroprostheses are widely investigated in behaving non-human primates, but technical constraints have limited progress in optimizing performance. In particular, the organization of movement-related neuronal activity across cortical layers remains poorly understood due, in part, to the widespread use of fixed-geometry multielectrode arrays. In this study, we use chronically implanted multielectrode arrays with individually movable electrodes to examine how the encoding of movement goals depends on cortical depth. In a series of recordings spanning several months, we varied the depth of each electrode in the prearcuate gyrus of frontal cortex in two monkeys as they performed memory-guided eye movements. We decode eye movement goals from local field potentials (LFPs) and multiunit spiking activity recorded across a range of depths up to 3 mm from the cortical surface. We show that both LFP and multiunit signals yield the highest decoding performance at superficial sites, within 0.5 mm of the cortical surface, while performance degrades substantially at sites deeper than 1 mm. We also analyze performance by varying bandpass filtering characteristics and simulating changes in microelectrode array channel count and density. The results indicate that the performance of LFP-based neuroprostheses strongly depends on recording configuration and that recording depth is a critical parameter limiting system performance.

Synchronized Activity between the Ventral Hippocampus and the Medial Prefrontal Cortex during Anxiety

The ventral hippocampus, unlike its dorsal counterpart, is required for anxiety-like behavior. The means by which it acts are unknown. We hypothesized that the hippocampus synchronizes with downstream targets that influence anxiety, such as the medial prefrontal cortex (mPFC). To test this hypothesis, we recorded mPFC and hippocampal activity in mice exposed to two anxiogenic arenas. Theta-frequency activity in the mPFC and ventral, but not dorsal, hippocampus was highly correlated at baseline, and this correlation increased in both anxiogenic environments. Increases in mPFC theta power predicted avoidance of the aversive compartments of each arena and were larger in serotonin 1A receptor knockout mice, a genetic model of increased anxiety-like behavior. These results suggest a role for theta-frequency synchronization between the ventral hippocampus and the mPFC in anxiety. They are consistent with the notion that such synchronization is a general mechanism by which the hippocampus communicates with downstream structures of behavioral relevance.

The Electrocortical Effects of Enflurane: Experiment and Theory

High concentrations of enflurane will induce a characteristic electroencephalogram pattern consisting of periods of suppression alternating with large short paroxysmal epileptiform discharges (PEDs). In this study, we compared a theoretical computer model of this activity with real local field potential (LFP) data obtained from anesthetized rats. After implantation of a high-density 8 x 8 electrode array in the visual cortex, the patterns of LFP and multiunit spike activity were recorded in rats during 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentration (MAC) enflurane anesthesia. These recordings were compared with computer simulations from a mean field model of neocortical dynamics. The neuronal effect of increasing enflurane concentration was simulated by prolonging the decay time constant of the inhibitory postsynaptic potential (IPSP). The amplitude of the excitatory postsynaptic potential (EPSP) was modulated, inverse to the neocortical firing rate. In the anesthetized rats, increasing enflurane concentrations consistently caused the appearance of suppression pattern (>1.5 MAC) in the LFP recordings. The mean rate of multiunit spike activity decreased from 2.54/s (0.5 MAC) to 0.19/s (2.0 MAC). At high MAC, the majority of the multiunit action potential events became synchronous with the PED. In the theoretical model, prolongation of the IPSP decay time and activity-dependent EPSP modulation resulted in output that was similar in morphology to that obtained from the experimental data. The propensity for rhythmic seizure-like activity in the model could be determined by analysis of the eigenvalues of the equations. It is possible to use a mean field theory of neocortical dynamics to replicate the PED pattern observed in LFPs in rats under enflurane anesthesia. This pattern requires a combination of a moderately increased total area under the IPSP, prolonged IPSP decay time, and also activity-dependent modulation of EPSP amplitude.

Effect of deep brain stimulation of the subthalamic nucleus upon the contralateral subthalamic nucleus in Parkinson disease

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an effective treatment of idiopathic Parkinson disease (PD). Exactly how HFS works remains unclear. Although HFS of the STN is most effective in improving contralateral motor functions, clinical studies have shown bilateral beneficial effects suggesting that unilateral STN HFS affects both ipsilateral and contralateral basal ganglia networks. In this study we evaluated the effect of STN HFS upon the contralateral STN in 14 PD subjects. The neural recordings were done during stereotaxic neurosurgery for implantation of deep brain stimulation electrodes in the second STN. Neuronal activity of the STN was analyzed before and during two minutes of HFS. There was a significant increase in the multiunit spiking activity of the STN during HFS in the contralateral STN. Our study provides direct electrophysiological evidence that the STN HFS is associated with increased activity of the contralateral STN. These findings suggest that increased STN output underlies therapeutic mechanisms of action of HFS.

Discrete- and continuous-time probabilistic models and algorithms for inferring neuronal UP and DOWN states.

UP and DOWN states, the periodic fluctuations between increased and decreased spiking activity of a neuronal population, are a fundamental feature of cortical circuits. Understanding UP-DOWN state dynamics is important for understanding how these circuits represent and transmit information in the brain. To date, limited work has been done on characterizing the stochastic properties of UP-DOWN state dynamics. We present a set of Markov and semi-Markov discrete- and continuous-time probability models for estimating UP and DOWN states from multiunit neural spiking activity. We model multiunit neural spiking activity as a stochastic point process, modulated by the hidden (UP and DOWN) states and the ensemble spiking history. We estimate jointly the hidden states and the model parameters by maximum likelihood using an expectation-maximization (EM) algorithm and a Monte Carlo EM algorithm that uses reversible-jump Markov chain Monte Carlo sampling in the E-step. We apply our models and algorithms in the analysis of both simulated multiunit spiking activity and actual multi- unit spiking activity recorded from primary somatosensory cortex in a behaving rat during slow-wave sleep. Our approach provides a statistical characterization of UP-DOWN state dynamics that can serve as a basis for verifying and refining mechanistic descriptions of this process.

Anterograde transneuronal viral tract tracing reveals central sensory circuits from white adipose tissue

The origins of the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) have been defined using the transneuronal viral retrograde tract tracer, pseudorabies virus. Activation of this SNS innervation is acknowledged as the principal initiator of WAT lipolysis. The central control of WAT lipolysis may require neural feedback to a brain-SNS-WAT circuit via WAT afferents. Indeed, conventional tract tracing studies have demonstrated that peripheral pseudounipolar dorsal root ganglion (DRG) sensory cells innervate WAT. The central nervous system projections of WAT afferents remain uncharted, however, and form the focus of the present study. We used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer, to define the afferent circuits projecting from WAT to the central nervous system. Siberian hamster inguinal (IWAT) or epididymal WAT was injected with H129 and the neuraxis processed for HSV-1 immunoreactivity. We found substantial overlap in the pattern of WAT sensory afferent projections with multiple SNS outflow sites along the neuraxis, suggesting the possibility of WAT sensory-SNS circuits that could regulate WAT SNS drive and thereby lipolysis. Previously, we demonstrated that systemic 2-deoxy-d-glucose (2DG) elicited increases in the SNS drive to IWAT. Here, we show that systemic 2DG administration also significantly increases multiunit spike activity arising from decentralized IWAT afferents. Collectively, these data provide structural and functional support for the existence of a sensory WAT pathway to the brain, important in the negative feedback control of lipid mobilization.

Effects of Familiarity on Neural Activity in Monkey Inferior Temporal Lobe

Long-term familiarity facilitates recognition of visual stimuli. To better understand the neural basis for this effect, we measured the local field potential (LFP) and multiunit spiking activity (MUA) from the inferior temporal (IT) lobe of behaving monkeys in response to novel and familiar images. In general, familiar images evoked larger amplitude LFPs whereas MUA responses were greater for novel images. Familiarity effects were attenuated by image rotations in the picture plane of 45 degrees. Decreasing image contrast led to more pronounced decreases in LFP response magnitude for novel, compared with familiar images, and resulted in more selective MUA response profiles for familiar images. The shape of individual LFP traces could be used for stimulus classification, and classification performance was better for the familiar image category. Recording the visual and auditory evoked LFP at multiple depths showed significant alterations in LFP morphology with distance changes of 2 mm. In summary, IT cortex shows local processing differences for familiar and novel images at a time scale and in a manner consistent with the observed behavioral advantage for classifying familiar images and rapidly detecting novel stimuli.

Looming Biases in Monkey Auditory Cortex

Looming signals (signals that indicate the rapid approach of objects) are behaviorally relevant signals for all animals. Accordingly, studies in primates (including humans) reveal attentional biases for detecting and responding to looming versus receding signals in both the auditory and visual domains. We investigated the neural representation of these dynamic signals in the lateral belt auditory cortex of rhesus monkeys. By recording local field potential and multiunit spiking activity while the subjects were presented with auditory looming and receding signals, we show here that auditory cortical activity was biased in magnitude toward looming versus receding stimuli. This directional preference was not attributable to the absolute intensity of the sounds nor can it be attributed to simple adaptation, because white noise stimuli with identical amplitude envelopes did not elicit the same pattern of responses. This asymmetrical representation of looming versus receding sounds in the lateral belt auditory cortex suggests that it is an important node in the neural network correlate of looming perception.

Detection of the subthalamic nucleus in microelectrographic recordings in Parkinson disease using the high-frequency (> 500 Hz) neuronal background

Accurate and fast localization of the subthalamic nucleus (STN) during intraoperative electrophysiological monitoring can improve the outcome of deep brain stimulation surgery. The authors show a simple method of detecting the STN that is based on an analysis of the high-frequency (> 500 Hz) background (HFB) activity of neurons. The HFB reflects multiunit spiking activity close to the recording electrode, and its characteristic profile, which is higher in the STN than in neighboring structures, and facilitates delineation of both the dorsal and ventral STN borders.

Cortical responses to cochlear implant stimulation: channel interactions.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

Opioid receptors mediate a postsynaptic facilitation and a presynaptic inhibition at the afferent synapse of axolotl vestibular hair cells

This study was designed to determine the effects of opiate drugs on the electrical activity of afferent neurons and on the ionic currents of hair cells from semicircular canals. Experiments were done on larval axolotls ( Ambystoma tigrinum). The multiunit spike activity of afferent neurons was recorded in the isolated inner ear under both resting conditions and mechanical stimulation. Ionic currents were recorded using voltage clamp of hair cells isolated from the semicircular canal. In the isolated inner-ear preparation, microperfusion of either non-specific opioid receptor antagonist naloxone (10 nM to 1 mM), μ receptor agonist [D-Ala 2, N-Me-Phe 4,Gly 5-ol]-enkephalin (1 pM to 10 μM), or κ receptor antagonist nor-binaltorphimine (10 nM to 100 μM) elicited a dose-dependent long-lasting (>5 min) increase of the electrical discharge of afferent neurons. The μ receptor agonist funaltrexamine (1 nM to 100 μM) and the κ receptor agonist U-50488 (1 nM to 10 μM) diminished the basal spike discharge of vestibular afferents. The δ receptor agonist D-Pen 2-D-Pen 5-enkephalin (1 nM to 10 mM) and the antagonist naltrindole (1 nM to 10 mM) were without a significant effect. The only drug that displayed a significant action on hair-cell ionic currents was trans-(±)-3,4-dichloro- N -methyl- N -(2-[1-pyrrolidinyl]-cyclohexyl) benzeneacetamide methanesulfonate (U-50488) that reduced the Ca 2+ current in a dose-dependent fashion. On its own, μ receptor agonist [D-Ala 2, N-Me-Phe 4,Gly 5-ol]-enkephalin (0.01 and 10 μM) significantly potentiated the response of afferent neurons to the excitatory amino acid agonist (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (0.1 μM), while synaptic transmission was blocked by the use of high-Mg 2+, low-Ca 2+ solutions. Our data indicate that the activity of vestibular afferent neurons may be regulated in a complex fashion by opioid receptors: μ opioid receptors mediating an excitatory, postsynaptic modulatory input to afferent neurons, and κ receptors mediating an inhibitory, presynaptic input to hair cells.

Principles of linear and angular vestibuloocular reflex organization in the frog.

We compared the spatial organization patterns of linear and angular vestibuloocular reflexes in frogs by recording the multiunit spike activity from cranial nerve branches innervating the lateral rectus, the inferior rectus, or the inferior obliquus eye muscles. Responses were evoked by linear horizontal and/or vertical accelerations on a sled or by angular accelerations about an earth-vertical axis on a turntable. Before each sinusoidal oscillation test in darkness, the static head position was systematically altered to determine those directions of horizontal linear acceleration and those planes of angular head oscillation that were associated with minimal response amplitudes. Inhibitory response components during angular accelerations were clearly present, whereas inhibitory response components during linear accelerations were absent. Likewise was no contribution from the vertical otolith organs (i.e., lagena and saccule) observed during vertical linear acceleration. Horizontal linear acceleration evoked responses that originated from eye muscle-specific sectors on the contralateral utricular macula. The sectors of the inferior obliquus and lateral rectus muscles on the utricle had an opening angle of 45 and 60 degrees, respectively and overlapped to a large extent in the laterorostral part of the utricle. Both sectors were coplanar with the horizontal semicircular canals. The sector of the inferior rectus muscle was narrow (opening 5 degrees), laterocaudally oriented, and slightly pitched up by 6 degrees. Angular acceleration evoked maximal responses in the inferior obliquus muscle nerve that originated from the ipsilateral horizontal and the contralateral anterior vertical canals in a ratio of 50:50. Lateral rectus excitation originated from the contralateral horizontal and anterior vertical semicircular canals in a ratio of 80:20. The excitatory responses of the inferior rectus muscle nerve originated exclusively from the contralateral posterior vertical canal. Measured data and known semicircular canal plane vectors were used to calculate the spatial orientation of maximum sensitivity vectors for the investigated eye muscle nerves in semicircular canal coordinates. Comparison of the directions of maximal sensitivity vectors of responses evoked by linear or angular accelerations in a given eye muscle nerve showed that the two vector directions were oriented about orthogonally with respect to each other. With this arrangement the linear and the angular vestibuloocular reflex can support each other dynamically whenever they are co-activated without a change in the spatial response characteristics. The mutual adaptation of angular and linear vestibuloocular reflexes as well as the differences in their organization described here for frogs may represent a basic feature common for vertebrates in general.

How neurons become BOLD?

Neuroimaging, particularly fMRI, has become a popular tool for studying brain function in humans. The assumption of the method is that the activity within regional populations of neurons is reflected in the fMRI response, namely the blood oxygen level-dependent or ‘BOLD’ signal. At last, almost a decade after the introduction of fMRI, this assumption has been tested directly.Logothetis et al. 1xNeurophysiological investigation of the basis of the fMRI signal. Logothetis, N.K. et al. Nature. 2001; 412: 150–157Crossref | PubMed | Scopus (3134)See all References1 simultaneously scanned and recorded from cortex in anaesthetized monkeys, using fMRI and electrophysiological recording. The monkeys viewed moving checkerboard patterns while electrodes placed in primary visual cortex measured single- and multi-unit neural spiking activity, as well as local field potentials (LFPs), which reflect the dendro-somatic inputs of the neural population. Simultaneous fMRI scanning was used to define a region of interest near the electrode tip that showed a significant BOLD response to the stimulus. The BOLD response was significantly correlated only with the LFPs, which were stronger and more sustained than the single- and multi-unit spiking activity. However, the signal-to-noise ratio of the fMRI signal was at least an order of magnitude weaker than the LFPs.These results indicate that the BOLD signal does indeed reflect an increase in neural activity. However, the difference between what the two techniques measure suggests that caution is warranted in making direct comparisons. Specifically, the correlation between BOLD and LFPs, rather than action potentials, suggest that the fMRI signal largely reflects the input and local processing within an area rather than the spiking output. Thus, it might be possible to observe a BOLD response in an area that has no single-unit activity measured electrophysiologically, particularly if the input is primarily modulatory. Furthermore, given the weak signal-to-noise ratio of the fMRI signal, a lack of fMRI activity does not necessarily imply an absence of neural activity. Although these caveats limit direct comparisons between physiology and neuroimaging data, the two techniques together offer a more comprehensive picture of the neural activity and circuitry than either can alone. And future imaging studies can proceed with the confidence that what they measure does indeed reflect real changes in neuronal activity.

Neurophysiological investigation of the basis of the fMRI signal.

Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.

2107 Differential responses of temporal patterns of sleep/waking cycles and multi-unit activities of suprachiasmatic nucleus and other brain regions toward

Scalp-derived human somatosensory evoked potentials (SEPs) contain high-frequency oscillations (600 Hz; ‘sigma-burst’) reflecting concomitant bursts of spike responses in primary somatosensory cortex that repeat regularly at 600 Hz. Notably, recent human intracranial SEP have revealed also 1 kHz responses (‘kappa-burst’), possibly reflecting non-rhythmic spiking summed over multiple cells (MUA: multi-unit activity). However, the non-invasive detection of EEG signals at 1 kHz typical for spikes has always been limited by noise contributions from both, amplifier and body/electrode interface. Accordingly, we developed a low-noise recording set-up optimised to map non-invasively 1 kHz SEP components.SEP were recorded upon 4 Hz left median nerve stimulation in 6 healthy human subjects. Scalp potentials were acquired inside an electrically and magnetically shielded room using low-noise custom-made amplifiers. Furthermore, in order to reduce thermal Johnson noise contributions from the sensor/skin interface, electrode impedances were adjusted to ⩽1 kΩ. Responses averaged after repeated presentation of the stimulus (n = 4000 trials) were evaluated by spatio-temporal pattern analyses in complementary spectral bands.Three distinct spectral components were identified: N20 (<100 Hz), sigma-burst (450–750 Hz), and kappa-burst (850–1200 Hz). The two high-frequency bursts (sigma, kappa) exhibited distinct and partially independent spatiotemporal evolutions, indicating subcortical as well as several cortical generators.Using a dedicated low-noise set-up, human SEP ‘kappa-bursts’ at 1 kHz can be non-invasively detected and their scalp distribution be mapped. Their topographies indicate a set of subcortical/cortical generators, at least partially distinct from the topography of the 600 Hz sigma-bursts described previously.The non-invasive detection and surface mapping of 1 kHz EEG signals presented here provides an essential step towards non-invasive monitoring of multi-unit spike activity.

Repeated tetanic stimulation in piriform cortex in vitro: epileptogenesis and pharmacology.

1. Focal cortical epilepsy was investigated by applying tetanic stimulation repeatedly (100 Hz. 2 s in duration, once every 10 min, 10 episodes) to layer III association fibers in rat piriform cortex slices and recording both extracellular and intracellular responses from the endopiriform nucleus. To promote excitability, piriform slices were incubated in artificial cerebrospinal fluid (ACSF) containing 0.9 mM Mg2+ and 5 mM K+, at an initial temperature of 10-12 degrees C, which was allowed to warm passively to room temperature. 2. Responses recorded extracellularly in the endopiriform nucleus consisted of two types: weak stimulation evoked an early-occurring, small-amplitude, negatively deflecting potential; strong stimulation evoked a more complex response comprising both an early potential of maximal amplitude and a later-occurring epileptiform potential of greater amplitude and longer duration. Late-occurring epileptiform potentials were not observed in slices incubated in ACSF at room temperature. 3. Both the early potential and the late-occurring epileptiform responses were abolished by the non-N-methyl-D-aspartic acid (non-NMDA) subtype of glutamate receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM). Application of D(-)-2-amino-5-phosphonopentanoic acid (APV; 50 microM) to block NMDA receptors was without effect on the early potential but diminished the late-occurring epileptiform potential. The late-occurring potential was unable to follow stimulation delivered at a frequency of 1 Hz. These results suggest that the early potential was generated monosynaptically and dependent solely on the activation of non-NMDA receptors, whereas the late-occurring epileptiform potential was polysynaptic in origin and possessed both a CNQX- and an APV-sensitive component. 4. Responses increased progressively in both amplitude and duration after tetanic stimulation. The threshold intensity required to evoke the complex dual-component potential was reduced by tetanic stimulation. An increase in multiunit spiking activity, indicating an increase in synchronous discharges, was also observed. A residual potential could be evoked in the presence of CNQX (10 microM) after the tetanic stimulation procedure. 5. Spontaneous discharges occurred as early as after the first episode of tetanic stimulation and persisted for the duration of the experiment. Spontaneous discharges were abolished by either CNQX or by a fourfold increase in extracellular Mg2+ concentration, the latter reversibly. APV reduced the frequency of spontaneous discharges by 38.6 +/- 9.3% (mean +/- SE). The conventional anticonvulsant drug 5,5-diphenylhydantoin, the benzodiazepine receptor agonist midazolam, and the benzodiazepine receptor antagonist flumazenil were without effect on the frequency of spontaneous discharges. Evoked responses were also unaffected by either 5,5-diphenylhydantoin or midazolam. Slices not exposed to cold ACSF, although demonstrating potentiation of evoked responses after tetanization did not produce spontaneous epileptiform discharges. 6. Intracellular recordings from endopiriform neurons revealed the cellular correlates of the extracellular responses. Weak stimulation evoked a small-amplitude depolarizing potential. Increasing the intensity of stimulation increased the amplitude of this response and also evoked a second depolarizing potential of greater amplitude occurring at variable latencies. Maximal stimulation evoked an action potential. After tetanic stimuli, responses resembling a paroxysmal depolarizing shift consisting of a depolarizing potential with superimposed multiple action potentials were evoked reliably. Passive membrane properties after repeated tetanic stimulation were not different when compared with control. 7. This novel model of in vitro focal cortical epilepsy has many features characteristic of conventional kindling including 1) progressive nature; 2) reduced threshold to evoke discharges; and 3) persist

Asymmetric sigmoid non-linearity in the rat olfactory system

The statistical relationship between multi-unit spike activity and simultaneously recorded local dendritic field potentials in the olfactory system of the waking rat was studied with chronically placed electrodes. The relationship had the form of a sigmoid increase in axonal firing probability conditional on the amplitude of dendritic potentials. These data were fitted with an asymmetric sigmoid curve previously derived from the Hodgkin-Huxlwy equations. The curve was fitted using non-linear regression to optimize its parameter: the maximal firing rate. The maximal rate also gave the steepness of the slope of the sigmoid. Pulse trains were recorded from excitatory and inhibitory neurons in the olfactory cortex (including the anterior olfactory nucleus, the prepyriform cortex and the lateral entorhinal area) as identified by the phase relations of the pulse probability and the dendritic potentials, and from the excitatory neurons in the bulb (the inhibitory granule cells do not give extracellularly detectable action potentials). All these neurons are known to interact in disynaptic negative feedback loops giving rise to oscillations. The same sigmoid function fit the data from both types of neurons in all locations. The curves for neurons in all parts of the olfactory cortex had a 3-fold higher slope and maximal value than the curves from bulbar neurons. The significances of this differences and of the asymmetric sigmoid are discussed in terms of models for olfactory oscillatory dynamics and pattern recognition.

Quantitative comparison of frequency representation in the auditory brainstem nuclei of the gerbil, Pachyuromys duprasi

Frequency representation in the auditory brainstem nuclei of the fattailed gerbil (Pachyuromys duprasi) was studied by focal iontophoretic HRP injections into the cochlear nucleus at physiologically characterized positions. Tuning curves of cochlear nucleus neurons were determined by extracellular recording of multi-unit spike activity prior to HRP application. Neurons with characteristic frequencies of 0.55 to 17.5 kHz were recorded. Anterograde labeling of synaptic terminal fields demonstrated a tonotopic arrangement of frequencies within the cochlear nucleus subdivisions and the lateral and medial superior olivary nuclei. In all nuclei investigated terminal fields were arranged in isofrequency planes. In the subdivisions of the cochlear nucleus and in the lateral superior olive the frequency range from 0.55 to 17.5 kHz was represented. In the medial superior olive on the other hand, frequency representation was restricted to frequencies below 3.5 kHz. Quantitative evaluation of tonotopy showed that the frequency representation in the anteroventral and posteroventral cochlear nucleus and lateral superior olive were very similar. The amount of tissue-volume processing one octave varied within the hearing range. The frequency range of highest auditory sensitivity (between 1 and 5 kHz) occupied up to 25% nuclear tissue/octave, while at the upper and lower limits of the hearing range, frequencies were represented by a ratio of 10-15% nuclear tissue/octave. The frequency representation pattern in these brainstem nuclei reflected exactly the frequency place map of the cochlea.

Gamma aminobutyric acid mediates ventromedial hypothalamic mechanisms controlling the execution of lordotic responses in the female rat

To study the participation of γ-aminobutyric acid (GABA) in the control of sexual behavior in the female rat, the effect of GABA and picrotoxin injections in the ventromedial hypothalamic nucleus (VMN) upon lordosis frequency and multiunit spike activity (MUSA) was determined. Infusion of 100 μg GABA into conscious rats reduced lordotic responsiveness within 15 min after injection; with a similar time course, the same dose markedly reduced MUSA in urethane anesthetized rats. Forty-five min after injection lordotic responsiveness recuperated to preinjection levels; at this time MUSA showed a rebound increase in neuron firing frequency. The possible relation between ventromedial hypothalamic neuronal activity and capacity for lordotic responses was further tested with injections of a local anesthetic: 1 μl of 2% Xylocaine infused into the VMN produced similar results, suppressing MUSA and lordotic responsiveness for ca. 45 min beginning immediately after injection. Microinjections of GABA antagonist picrotoxin had the opposite effects: 0.1 μg increased MUSA and lordotic responsiveness at 5 and 45 min; however at 20 min, when MUSA was at its highest, lorosis frequency was not elevated. Injections of solvent had no consistent effects on either measure. Two conclusions many be tentatively drawn from these data: (a) the VMN is the origin of a neural signal which exerts a moment-to-moment gating control on the execution of lordosis, and (b) the generation and/or the output of this signal is under the control of a GABAergic hypothalamic mechanism which normally exerts an inhibitory effect on the display of lordotic responses.

Changes in rubral multiunit activity after lesions in the interpositus nucleus of the cat

The initial effect of an acute lesion in the central nervous system is loss of neural function. With time, however, restorative processes, generally termed 'compensation', may result in some degree of recovery of neural function. The mechanisms involved in recovery may include morphological changes in synaptic connections, a process described as neuroplasticity. Direct evidence for neuroplasticity in the mature mammalian central nervous system has been presented (for recent reviews, see refs. 3-6). Electrophysiological studies of the rubrospinal tract in the cat have shown evidence of neuroplasticity in which sprouting of axonal terminals (collateral sprouting) is thought to occur in the red nucleus following partially deafferenting lesions ~4. The demonstration of synaptic reorganization in this nucleus is based on evidence that the two major inputs to this nucleus, corticorubral and interpositorubral fibers, make synaptic connection with two separate portions of the membranes of rubral neurons. Tsukahara and co-workers12, la showed in the intact cat that excitatory postsynaptic potentials (EPSPs) evoked in rubral neurons by stimulating the ipsilateral pericruciate cortex had relatively slow rise times, long decay phases, and low peak amplitudes. EPSPs evoked by stimulating the contralateral interpositus nucleus displayed more rapid rise times, shorter decay phases, and greater peak amplitudes. They attributed these differences to segregation of synaptic terminals on rubral neurons, cortical fibers on distal dendrites and interpositus fibers on proximal dendrites and somas. The reorganization of cortical synaptic contacts on rubral neurons after partial deafferenration was investigated in chronic cats with lesions of the contralateral interpositus nucleus 14. They observed a progressive shortening of the rise times of cortically evoked EPSPs for 4~10 days after the lesions and no further change after longer intervals. These changes in cortically evoked EPSPs were thought to result from collateral sprouting of cortical fibers to innervate more proximal portions of rubral neurons. If neuroplasticity participates in the recovery of motor function after a lesion, it must do so not only through changes in postsynaptic potentials, but also through changes in patterns of spike activity directed toward brain stem and spinal nuclei. It is not clear what effect changes in EPSP wave forms may have on rubral spike activity. We have investigated this issue by recording spontaneous multiunit spike activity in