Metabolic changes in the superior colliculus after retinal receptor loss—Neurotrophic interactions in the inactive visual system

In the mature rat, direct denervation by means of eye enucleation resulted in a temporary metabolic depression followed by "recovery" in primary visual centers as determined by the 2-deoxyglucose technique (4). After unilateral destruction of the retinal receptor layer by means of intense light, the superior colliculus (SC) demonstrated this same depression-recovery process. Because receptor destruction is believed to silence ongoing ganglion cell activity, and because the SC changes occurred whether or not ganglion cells sustained damage, it appeared that direct denervation of colliculus neurons was not necessary to initiate the depression-recovery sequence and that lack of activity or "disuse" was the critical factor. The silencing effect of the receptor destruction was confirmed when tetrodotoxin (TTX) injections into the damaged eye 2 months after damaging light exposure only slightly affected metabolic activity in the recovered colliculus. Binocular TTX injections in unilaterally light-damaged rats after 2 months of recovery resulted in greater depression in the normal colliculus than in the "recovered" colliculus, again suggesting that increases in glucose metabolism over time reflected physiological adjustments in the SC to loss of afferent activity. The strong depression in the SC fed by the normal eye after TTX injection confirmed that tonic retinal afferent activity was important to the metabolic integrity of the SC and that cessation of such activity could lead to at least to depression in the system. In a final group of 2-month recovery animals the light-damaged eye was enucleated. Presumably, if withdrawal of afferent activity is solely responsible for initiating the depression-recovery sequence, the destruction of already silenced retinal ganglion cells would have no effect on the recovered SC. This was not found to be the case. In fact, enucleation reinstated the metabolic depression in the recovered SC and demonstrated that denervation per se resulted in depression of glucose metabolism in postsynaptic neurons. Even in the absence of impulse activity, visual system neurons maintained trophic interactions.     

Effects of kainic acid and other excitotoxins in the rat superior colliculus: Relations to glutametergic afferents

In this study we have performed surgical, chemical and combined surgical/chemical lesions in order to elucidate neurotransmitter mechanisms in the superior colliculus (SC) of albino rats. Visual cortex (VC) ablation reduced high affinity (HA) uptake ofd-Asp by 32% in the deafferented SC. Local injection of kainic acid (KA) into SC reduced HAd-Asp uptake selectively in the lower dose range (< 1nmol) by 50–60%. The GABAergic marker glutamate decar☐ylase (GAD) was decreased by maximally 60% only at doses exceeding 2 nmol. Choline acetyltransferase (ChAT), however, was not affected at any of the doses administered. VC ablation provided an almost complete protection against 1 nmol KA. When KA was injected 2 days prior to VC ablation an additive effect on HAd-Asp uptake of the two lesions was observed. From these observations we infer that the notion of a glutamatergic projection from VC to SC has been strengthened. Moreover, local neurons in intermediate layers account for about 60% of the HAd-Asp uptake in SC, and these are most likely impinged upon by the glutamatergic afferents. The neurotoxic effects of KA were compared with those of some suspected endogenous excitotoxins, i.e. N-methyl tetrahydrofolic acid (Me-THF), other folates and the tryptophan metabolite quinolinic acid (QA). N-methyl tetrahydrofolic acid, Me-THF (4 and 10 nmol) reduced HAd-Asp uptake by about 50%, only when coinjected with ascorbic acid. GAD and ChAT were not affected at either of the doses. QA was about 100-fold less potent than KA on a molar basis, and the maximal reduction of GAD was similar in QA and KA injected animals, whereas the maximal reduction of HAd-Asp was only 40% after QA injection in SC. We conclude that Me-THF, QA and KA exert their neurotoxic actions by different mechanisms as judged by the behavioral, histopathological and biochemical sequelae seen after local injections of the respective substances in intermediate layers of SC and corroborate data obtained from other brain areas.     

Effects of kainic acid and other excitotoxins in the rat superior colliculus: relations to glutamatergic afferents

In this study we have performed surgical, chemical and combined surgical/chemical lesions in order to elucidate neurotransmitter mechanisms in the superior colliculus (SC) of albino rats. Visual cortex (VC) ablation reduced high affinity (HA) uptake of D-Asp by 32% in the deafferented SC. Local injection of kainic acid (KA) into SC reduced HA D-Asp uptake selectively in the lower dose range (less than 1 nmol) by 50-60%. The GABAergic marker glutamate decarboxylase (GAD) was decreased by maximally 60% only at doses exceeding 2 nmol. Choline acetyltransferase (ChAT), however, was not affected at any of the doses administered. VC ablation provided an almost complete protection against 1 nmol KA. When KA was injected 2 days prior to VC ablation an additive effect on HA D-Asp uptake of the two lesions was observed. From these observations we infer that the notion of a glutamatergic projection from VC to SC has been strengthened. Moreover, local neurons in intermediate layers account for about 60% of the HA D-Asp uptake in SC, and these are most likely impinged upon by the glutamatergic afferents. The neurotoxic effects of KA were compared with those of some suspected endogenous excitotoxins, i.e. N-methyl tetrahydrofolic acid (Me-THF), other folates and the tryptophan metabolite quinolinic acid (QA). N-methyl tetrahydrofolic acid, Me-THF (4 and 10 nmol) reduced HA D-Asp uptake by about 50%, only when coinjected with ascorbic acid. GAD and ChAT were not affected at either of the doses. QA was about 100-fold less potent than KA on a molar basis, and the maximal reduction of GAD was similar in QA and KA injected animals, whereas the maximal reduction of HA D-Asp was only 40% after QA injection in SC. We conclude that Me-THF, QA and KA exert their neurotoxic actions by different mechanisms as judged by the behavioral, histopathological and biochemical sequelae seen after local injections of the respective substances in intermediate layers of SC and corroborate data obtained from other brain areas.     

Eye movement is controlled by basal ganglia-induced GABAergic inhibition

Saccadic eye movement is controlled by a midbrain structure, superior colliculus (SC). Cells in its intermediate layer show a burst of spikes before saccades to the contralateral disc. A major input to the SC comes from the substantia nigra pars reticulata (SNr). SNr cells are characterized by their high frequency tonic discharge. Many of them stop discharging before a contralateral saccade only when the saccade is made intentionally. The mirror image-like relationship between the SNr and the SC suggests that the nigro-collicular connection is inhibitory. To determine whether the nigro-collicular inhibition is necessary for normal eye movements, we injected a small amount of GABA-related substances into the SC or the SNr. Following injection of muscimol (GABA agonist) into the SC, contralateral saccades became delayed, hypometric and slower; the monkey finally became unable to make saccades. This result indicated that the SC is crucial for normal saccades and that SC cells have ample GABA receptors. Following injection of bicuculline (GABA antagonist), irrepressible saccades occurred repeatedly to the contralateral side, suggesting that SC cells are under tonic inhibition which is mediated by GABA. Similar involuntary saccades were induced by injection of muscimol into the SNr. This suggested that the SNr is the origin of the GABAergic tonic inhibition. These results suggested that the basal ganglia control the initiation of saccadic eye movement by changing the level of the nigro-collicular inhibition.     

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [14C]2-deoxyglucose study

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [14C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.     

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [C]2-deoxyglucose study

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [¹⁴C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.     

Fixation and orientation control by the tecto-reticulo-spinal system in the cat whose head is unrestrained

The role of the tecto-reticular and tecto-reticulo-spinal neurons (here called TR(S)Ns) in gaze control is described. TR(S)Ns, located in the deeper layers of the cat superior colliculus (SC), project onto the eye and head premotor circuitry. TR(S)Ns located in the caudal SC had sustained and phasic discharges related to the control of gaze movements. The sustained discharge occurred when the visual axis was positioned at some vector quantity away from a target of interest. Each cell has its preferred vector corresponding to the cell's location on the collicular retinotopic map. This tonic discharge acted as a preamble to the phasic discharge and served to pre-excite the relevant oculomotor circuitry. The phasic discharge preceded gaze shifts whose direction and magnitude matched the preferred vector. The intensity of this discharge was correlated to the acceleration and velocity of the movement. TR(S)Ns situated in the rostral SC were maximally active when the cat fixated a target of interest. These neurons decreased their discharge rate during gaze shifts. Thus, TR(S)Ns provide both fixation and orientation signals to the eye and head premotor circuitry. A scheme is proposed where TR(S)Ns lie within a gaze feedback loop that controls eye and head movements via inputs to long lead burst neurons and omnipause neurons.     

Changes in various activation indices as a function of the value given by a stimulus in anhedonic and deprossogenic subjects

The aim of this experiment was to investigate, in "normal" subjects, the relationship between personality characteristics (anhedonia and depressogenic attitudes) and various tonic and phasic activation indices (EEG power spectra, CNV (at Fz and Cz), heart rate and reaction time) recorded during auditory stimulations, and the influence of the affective value of stimuli on phasic activation indices. Eighteen subjects were divided into two opposite groups according to their scores on two self-rating questionnaires (the Chapman Physical Anhedonia Scale and the Beck-Weissman Dysfunctional Attitude Scale): the A group (anhedonic with depressogenic attitudes) and the H group (hedonic and non-depressogenic). The experiment was divided into three phases. The first and third phase utilised an identical classical CNV paradigm. During the second phase, two of the three neutral warning tones of the first phase were given, by conditioning, a positive or a negative value. The results showed that: 1) before conditioning, when all stimuli were neutral, all activation indices (tonic and phasic) were significantly higher in the A group than in the H group; 2) after conditioning, the two groups differed mainly by their cortical reactivity to the positively conditioned sound: the amplitude of the two CNV components increased in the H group whereas a tendency to a CNV decrease was seen in the A group; 3) all the between-group CNV differences were significant only at Fz. These results were discussed in terms of differences of optimal level of activation.     

Slow phasic and tonic activity of ventral pallidal neurons during cocaine self-administration

Ventral pallidal (VP) neurons exhibit rapid phasic firing patterns within seconds of cocaine-reinforced responses. The present investigation examined whether VP neurons exhibited firing rate changes: (1) over minutes during the inter-infusion interval (slow phasic patterns) and/or (2) over the course of the several-hour self-administration session (tonic firing patterns) relative to pre-session firing. Approximately three-quarters (43/54) of VP neurons exhibited slow phasic firing patterns. The most common pattern was a post-infusion decrease in firing followed by a progressive reversal of firing over minutes (51.16%; 22/43). Early reversals were predominantly observed anteriorly whereas progressive and late reversals were observed more posteriorly. Approximately half (51.85%; 28/54) of the neurons exhibited tonic firing patterns consisting of at least a two-fold change in firing. Most cells decreased firing during drug loading, remained low over self-administration maintenance, and reversed following lever removal. Over a whole experiment (tonic) timescale, the majority of neurons exhibited an inverse relationship between calculated drug level and firing rates during loading and post-self-administration behaviors. Fewer neurons exhibited an inverse relationship of calculated drug level and tonic firing rate during self-administration maintenance but, among those that did, nearly all were progressive reversal neurons. The present results show that, similar to its main afferent the nucleus accumbens, VP exhibits both slow phasic and tonic firing patterns during cocaine self-administration. Given that VP neurons are principally GABAergic, the predominant slow phasic decrease and tonic decrease firing patterns within the VP may indicate a disinhibitory influence upon its thalamocortical, mesolimbic, and nigrostriatal targets during cocaine self-administration.     

Determinants of patchy metabolic labeling in the somatosensory cortex of cats: a possible role for intrinsic inhibitory circuitry

Despite repeated experimental demonstration that somatic stimulation leads to an intermittent, "column-like" pattern of 2-deoxyglucose (2DG) label in the somatosensory cortex, the functional significance of this pattern remains uncertain. A number of recent studies have suggested that the putative inhibitory neurotransmitter GABA may play an influential role in the cortical processing of sensory information. To test the possibility that GABA-mediated inhibitory processes might participate in the formation of the 2DG patches, the 2DG pattern obtained under "normal" experimental conditions was compared with the pattern observed when cortical inhibition was modified by topical application of the GABA antagonist, bicuculline methiodide (BIC). Under "normal" experimental conditions, we found that somatic stimulation led to an intermittent, patch like distribution of 2DG uptake in cat somatosensory cortex, which exhibited consistent features in animals studied using the same stimulus and experimental condition. Reconstructions of the stimulus-evoked activity patterns revealed that the label was confined to territories known to receive input from the stimulated body region and was organized into elongated strips. Topical application of BIC to the somatosensory cortex dramatically altered the dimension of the metabolic patches, which were often embedded in a field of elevated 2DG uptake. In BIC-treated hemispheres the average width of 2DG patches was 1266 microns, whereas the average width of patches in the opposite untreated hemisphere (elicited by identical stimuli) was 713 microns. Unfolded maps of the labeling pattern revealed that in the BIC-treated hemispheres adjacent "strips" of 2DG label tended to fuse, leading to a less intermittent distribution than that observed in the untreated hemispheres. An important role for GABA in the formation of the normal cortical response to somatic stimulation is suggested.     

Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions

A series of experiments was carried out using 14C-2-deoxy-d-glucose (DG) in order to examine the functional architecture of macaque striate (primary visual) cortex. This paper describes the results of experiments on uptake during various baseline (or reference) conditions of visual stimulation (described below), and on differences in the functional architecture following monocular versus binocular viewing conditions. In binocular "baseline" experiments, monkeys were stimulated either (1) in the dark, (2) with a diffuse gray screen, or (3) with a very general visual stimulus composed of gratings of varied orientation and spatial frequency. In all of these conditions, DG uptake was found to be topographically uniform within all layers of parafoveal striate cortex. In monocular experiments that were otherwise similar, uptake was topographically uniform within the full extent of the eye dominance strip, in all layers. Certain other visual stimuli produce high uptake in the blobs, and still another set of visual stimuli (including high-spatial-frequency gratings) produce highest uptake between the blobs at parafoveal eccentricities, even in an unanesthetized, unparalyzed monkey. Eye movements per se had no obvious effect on striate DG uptake. Endogenous uptake in the blobs (relative to that in the interblobs) appears higher in the squirrel monkey than in the macaque. The pattern of DG uptake produced by binocular viewing was found to deviate in a number of ways from that expected by linearly summing the component monocular DG patterns. One of the most interesting deviations was an enhancement of the representation of visual field borders between stimuli differing from each other in texture, orientation, direction, etc. This "border enhancement" was confined to striate layers 1-3 (not appearing in any of the striate input layers), and it only appeared following binocular, but not monocular, viewing conditions. The border enhancement may be related to a suppression of DG uptake that occurs during binocular viewing conditions in layers 2 + 3 (and perhaps layers 1 and 4B), but not in layers 4Ca, 4Cb, 5 or 6. Another major class of binocular interaction was a spread of neural activity into the "unstimulated" ocular dominance strips following monocular stimulation. Such an effect was prominent in striate layer 4Ca, but it did not occur in layer 4Cb. This "binocular" spread of DG uptake into the inappropriate eye dominance strip in 4Ca may be related to the appearance of orientation tuning and orientation columns in that layer. No DG effects were seen that depended on the absolute disparity of visual stimuli in macaque striate cortex.     

Reversible and irreversible damage to cochlear afferent neurons by kainic acid excitotoxicity

Kainic acid (KA) selectively damages afferent synapses that innervate, in chickens, mainly tall hair cells. To better understand the nature of KA-induced excitotoxic damage to the cochlear afferent neurons, KA, at two different concentrations (0.3 or 5 mM), was injected directly into the inner ear of adult chickens. Pathologic changes in the afferent nerve ending and cell body were evaluated with light and transmission electron microscopy at various time points after KA application. The compound action potential (CAP) and cochlear microphonic (CM) potential were recorded to monitor the physiologic status of the afferent neurons and hair cells, respectively. Hair cell morphology and function were essentially normal after KA treatment. However, afferent synapses beneath tall hair cells were swollen within 30 minutes after KA at both low (KA-L) and high (KA-H) doses. In the KA-L group, the swelling disappeared within 1 day and the morphology of the postsynaptic region returned to near normal condition. In the KA-H group, by contrast, the vacant region beneath tall hair cells remained evident even 20 weeks after KA. The number of cochlear ganglion neurons in the KA-H group decreased progressively from 1 to 8-20 weeks, whereas hair cells in the basilar papilla remained morphologically intact out to 20 weeks after KA. There was no significant change in neuron number in the KA-L group. Temporal changes in the CAP amplitude paralleled the anatomic changes, although the CAP only partially recovered. These results suggest that KA induces partially reversible damage to cochlear afferent neurons with low KA concentration; above this level, KA triggers irreversible, progressive neurodegeneration.     

Recruitment order of motor units in man: significance of pre-existing state of facilitation

It has been shown in previous investigations that the recruitment order of motor units is different in tonic and in phasic voluntary activity. The significance of the pre-existing state of facilitation in the motoneurone pool for the recruitment of units is studied, using the phasic flexion reflex in the anterior tibial muscle as test reflex. It is shown that the recruitment order of units in a series of reflexes (1) is unstable if the subject does not expect the stimulus; (2) is stable and identical with that in tonic activity if the subject subliminally facilitates the motoneurone pool before the reflex activation; (3) is stable and almost identical with that in tonic activity if the subject expects the stimulus and therefore involuntarily influences the motoneurone pool; (4) is stable and similar to that in phasic voluntary activity if the subject inhibits the motoneurone pool before the activation and the stimulus strength thus consequentially is increased; and (5) is influenced by blockade of the proprioceptive afferent impulses from the muscle. It is concluded that normal man can select in advance the recruitment order of motor units most appropriate for the work intended.     

Disturbances in the voluntary recruitment order of anterior tibial motor units in bradykinesia of Parkinsonism

The recruitment of motor units is studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies that the recruitment order is different in tonic and in phasic activities; in tonic activity the recruitment order is stable and low frequency units are always recruited before high frequency units; in phasic activity, however, the recruitment order is unstable and units with a higher frequency range may be recruited before units with lower frequency range. In this investigation the shifts between tonic and phasic recruitment order in voluntary contraction were compared in normal subjects and in patients with severe bradykinesia of Parkinsonism. Upon initiation of a voluntary contraction in a normal subject, phasic recruitment order may be used for a few 100 msec but tonic recruitment order then takes over. In bradykinetic patients, however, this shift from phasic to tonic recruitment order is delayed. After termination of tonic voluntary contraction in a normal subject, phasic recruitment order can again be used after a few seconds. In bradykinetic patients, however, the shift back from tonic to phasic recruitment order is also delayed. In favourable experimental situations the shift from phasic to tonic recruitment order can be normalized by passive stretch of the muscle and the shift from tonic to phasic recruitment pattern by unloading the muscle. It is discussed whether the pathological recruitment in bradykinesia might be due to disturbed gamma loop function.     

Differences in recruitment order of motor units in phasic and tonic flexion reflex in `spinal man''

The recruitment order of motoneurones in muscle contractions has been held to be largely constant and determined by the size of the cell. However, as shown in a previous investigation using electromyographic techniques, the order in which different motor units are activated during voluntary muscle contractions changes in normal human subjects on shifts from phasic to tonic contraction. In order to investigate these two types of activity also in cases in which the cerebral influence on the motoneurone pool is blocked, an analysis was made of the recruitment order in phasic and tonic flexion reflexes in 10 patients with total interruption of the spinal cord. The following four principles were found to apply and presumed to be generally valid for the isolated human spinal cord: (1) in the phasic exteroceptive reflex, the order of recruitment varies despite application of a standardized stimulus; (2) in the tonic reflex, the first unit to be recruited is usually the same even with widely different types of stimuli; (3) a shift from phasic to tonic reflex activation may result in considerable changes in recruitment order; (4) after facilitation by a subliminal long-lasting stimulus, the first unit to be recruited in the phasic reflex is also the first to be recruited in the tonic reflex. It is suggested that a tonic influence on the motoneurone pool is required for the presupposed constancy of the recruitment order.     

Phasic and tonic reflexes evoked in human antagonistic wrist muscles by tendon vibration

The electromyographic reflex responses of the voluntarily contracting wrist flexor and extensor muscles to periods of vibration-evoked enhanced, Ia-dominated afferent discharge from flexor carpi radialis (FCR) were studied in normal human subjects. Three main response phases were characterised, namely, (i) phasic 'on' responses elicited at the commencement of stimulation, (ii) tonic response levels occurring during prolonged stimulation and (iii) phasic 'off' responses elicited at the termination of stimulation. The phasic 'on' reflex responses of FCR and extensor carpi radialis (ECR) comprised, respectively, a peak of autogenetic excitation of group mean latency 18.8 ms and a trough of reciprocal inhibition of group mean latency 38.0 ms. Prolonged (2 s) trains of FCR (agonist) vibration evoked a phase of tonic reflex excitation in FCR whose mean level was significantly increased, by 20%, above pre-stimulus activity and which did not change over the 0.5-2.0 s vibration period. Progressive reduction of the duration (from 2000 ms to 100 ms) of vibration trains demonstrated that phasic disfacilitatory 'off' troughs regularly occurred, with a consistent latency (mean 24.2 ms), on withdrawal of each period of enhanced Ia-input. This indicates that the responsible excitatory reflex mechanism was operational for the entire duration of each of the vibration periods tested. The extra latency (on average 5.4 ms) of phasic 'off' relative to 'on' responses may be attributed to factors (e.g. 5-10 ms duration of unitary muscle action potentials and afterdischarge in reflex pathways) which inevitably delay the appearance of overt disfacilitatory reductions in EMG rather than the involvement of different reflex pathways. Thus, short-latency, possibly monosynaptic, reflex excitation contributed throughout the entire tonic excitatory response. Sustained FCR (antagonist) vibration produced a significant tonic reciprocal inhibitory reflex depression, by 7% pre-stimulus EMG, of ECR activity which remained steady during the 0.5-2.0 s vibration period. The absence of well-defined phasic disinhibitory 'off' responses in ECR suggests that the contribution of oligosynaptic reflex inhibitory mechanisms to the tonic suppression of activity occurring during continuing vibration is relatively small.     

Phasic and tonic firing properties in rat oculomotor nucleus motoneurons, studied in vitro

Alert-chronic studies show that ocular motoneurons (Mns) exhibit a phasic and tonic firing correlated with eye saccade-velocity and position (fixation), respectively. Differences in the phasic and tonic firing among Mns depend on synaptic inputs and/or the intrinsic membrane properties. We have used in vitro slice preparation to investigate the contribution of membrane properties to firing properties of Wistar rat oculomotor nucleus Mns. We recorded different discharge patterns and focused on Mns with sustained discharge (type I) because they were the most abundant, and their firing pattern resembles that reported in alert preparations. Various differences divided these Mns into types I(A) and I(B); the afterhyperpolarization (AHP) phase of the spike was monophasic in I(A) and biphasic in I(B); I(A) Mns showed tonic or phasic-tonic firing depending on the current intensity, while I(B) Mns showed phasic-tonic discharge; the phasic firing was higher in I(B) than in I(A) Mns; I(A) Mns fired in a narrower range than did I(B) Mns; and I(A) Mns showed lower maximum frequency than did I(B) Mns. In conclusion, I(A) and I(B) Mns show different phasic firing properties and dynamic range, supported by intrinsic membrane properties. We suggest that I(A) and I(B) Mns innervate fast-twitch muscle fibres with different contraction speeds, and could contribute to generating a fine phasic signal for a graded muscle contraction. Finally, we have demonstrated an inverse relationship between Mn thresholds and tonic firing gain, concluding that intrinsic membrane properties could not support the covariation between tonic firing gain and recruitment thresholds reported in alert studies.     

Functional anatomy of the second visual area (V2) in the macaque

To study the functional organization of secondary visual cortex (V2) in the primate, 14C-2-deoxy-d-glucose (DG) was injected while macaque monkeys were shown specific visual stimuli. Wherever possible, patterns of DG uptake were compared with the position of dark and light cytochrome oxidase (cytox) stripes (Tootell et al., 1983). Often, the DG effects of 2 different stimuli were compared in the same hemisphere to eliminate ambiguities inherent in between-animal comparisons. Data were obtained from a large number of animals in conjunction with related DG studies in area V1 (primary visual or striate cortex). The following conclusions were reached: (1) in some macaque monkeys, dark cytox stripes were faint or absent. Although this could conceivably be due to poor staining technique, some evidence suggests that the lack of enzyme stripe pattern is real. In all animals, including those that showed poor or no cytox staining evidence for stripes, the functional architecture revealed by the DG was consistently present and robust. (2) Uniform gray stimuli produce a relatively uniform pattern and minimal stimulus-related DG uptake. (3) Eye movements per se produce some uptake in the V2 stripes. (4) Very generalized visual stimulation conditions (e.g., binocular stimulation with a grating of varied orientation and varied spatial frequency) produced a pattern of uptake that is greatest in both sets of dark cytox stripes and lighter in the light cytochrome stripes. (5) In both the DG and cytox results, the V2 "stripes" are more accurately described as stripe-shaped collections of patches. (6) In almost all cases, DG patterns were columnar in shape, extending from white matter to cortical surface. The boundaries of the columns were most sharply defined, and the contrast was highest, in layers 3B/4, becoming slightly more blurry and lower in contrast in other layers. Laminar differences between DG patterns in V2 were almost negligible, compared with the profound laminar differences in macaque V1. (7) There is no DG evidence for, and much against, the possibility of an ocular dominance architecture in V2. (8) There are orientation columns in macaque V2. DG-labeled orientation columns are spaced further apart than those in V1, by a factor of about 1.6, but the columns are not correspondingly wider. (9) Spatially diffuse variations in color produce high uptake confined, at least largely, to the thin cytox stripes. (10) There is evidence for spatially antagonistic color surrounds in color cells in the thin stripes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrophysiological evidence of mediolateral functional dichotomy in the rat nucleus accumbens during cocaine self‐administration II: phasic firing patterns

In the cocaine self‐administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self‐administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (core, dorsal shell, ventromedial shell, ventrolateral shell, or rostral pole). Neural recording sessions were typically conducted on days 13–17 of cocaine self‐administration (0.77 mg/kg per 0.2‐mL infusion; fixed‐ratio 1 schedule of reinforcement; 6‐h daily sessions). Pre‐press rapid phasic firing rate changes were greater in lateral accumbal (core and ventrolateral shell) than in medial accumbal (dorsal shell and rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre‐press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre‐press rapid phasic activity, coupled with a greater prevalence of tonic increase firing, may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions.     

REM Sleep Microstates in the Human Anterior Thalamus

Rapid eye movement (REM) sleep is an elusive neural state that is associated with a variety of functions from physiological regulatory mechanisms to complex cognitive processing. REM periods consist of the alternation of phasic and tonic REM microstates that differ in spontaneous and evoked neural activity. Although previous studies indicate, that cortical and thalamocortical activity differs across phasic and tonic microstates, the characterization of neural activity, particularly in subcortical structures that are critical in the initiation and maintenance of REM sleep is still limited in humans. Here, we examined electric activity patterns of the anterior nuclei of the thalamus as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness in a group of epilepsy patients (N = 12, 7 females). Anterothalamic local field potentials (LFPs) showed increased high-α and β frequency power in tonic compared with phasic REM, emerging as an intermediate state between phasic REM and wakefulness. Moreover, we observed increased thalamocortical synchronization in phasic compared with tonic REM sleep, especially in the slow and fast frequency ranges. Wake-like activity in tonic REM sleep may index the regulation of arousal and vigilance facilitating environmental alertness. On the other hand, increased thalamocortical synchronization may reflect the intrinsic activity of frontolimbic networks supporting emotional and memory processes during phasic REM sleep. In sum, our findings highlight that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested by anterothalamic LFPs and thalamocortical synchronization.SIGNIFICANCE STATEMENT REM sleep is a heterogeneous sleep state that features the alternation of two microstates, phasic and tonic rapid eye movement (REM). These states differ in sensory processing, awakening thresholds, and cortical activity. Nevertheless, the characterization of these microstates, particularly in subcortical structures is still limited in humans. We had the unique opportunity to examine electric activity patterns of the anterior nuclei of the thalamus (ANTs) as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness. Our findings show that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested in the level of the thalamus and thalamocortical networks.