Neuronal activity in the monkey motor thalamus during bicuculline-induced dystonia

Recent data suggest that a decreased basal ganglia output may occur in dystonia, resulting in an increased thalamic drive to the mesial premotor cortex. In a previous work we found that injection of the GABAA antagonist bicuculline into the rostral motor thalamus induced contralateral dystonic postures, whereas myoclonic jerks were frequent after injection into the caudal motor thalamus. In the present study, we performed electrophysiological recordings in the rostral and caudal parts of the ventrolateral thalamus of two cynomolgus monkeys before and after bicuculline injections or saline injections. Discharge frequencies of thalamic neurons were increased after bicuculline injections vs. controls. Their discharge pattern was more bursty in the caudal part in which bursts of neuronal activity were correlated with myoclonic jerks. After bicuculline injection, neurons responded more frequently and less selectively to passive limb movements in both parts of the motor thalamus. Conversely, the response to microstimulation increased after bicuculline injection, particularly in the caudal part. Our data show that acute bicuculline-induced dystonia is associated with a reversible overactivity and disorganization of neuronal activity in the motor thalamus. Such a phenomenon might induce an overspreading of cortical activity leading to dystonia. We postulate that the distinct clinical syndromes observed after bicuculline injections into the rostral and caudal motor thalamus are due to differences both in the neuronal circuitry within each thalamic nucleus and in segregated cortical projections.     

Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo

Excitatory amino acid neurotransmitters, such as l-glutamate, act at several receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Extensive in vitro work indicates that both NMDA receptors and non-NMDA receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA receptors to epsps in vivo under physiological conditions is, however, almost unknown. The receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory amino acid receptor-mediated epsp in vivo involving both non-NMDA receptors and, in particular, NMDA receptors.     

Neuronal activity in the postcentral cortex related to force regulation during a precision grip task

Recordings from single neurons in the primary somatosensory cortex of the monkey during force regulation between the fingers showed following characteristics: the existence of classes of discharge patterns similar to those in motor cortex, but with differences in their distribution, a late onset of activity changes in relation to force increase and a linear relation to force, but with shallow mean rate-force slope.     

Reevaluation of the primary motor cortex connections with the thalamus in primates

Six injections (approximately 1 mm in diameter) of biotinylated dextran amine (BDA) were placed in different locations of the primary motor cortex of the rhesus monkey. Anterograde and retrograde labeling patterns in the thalamus were charted and individual labeled axons traced in continuous serial sections. Both anterograde and retrograde labeling in the thalamus was extensive, spanning several millimeters mediolaterally and including ventral lateral, ventral anterior, centromedian, and centrolateral nuclei. Paracentral, mediodorsal, lateral posterior, and medial pulvinar nuclei were also labeled. Two basic types of corticothalamic axons were identified: small to medium-width, type 1 axons that formed large terminal fields with small boutons, and thick, type 2 axons that formed small terminal fields with large boutons. Within each group, subtypes were identified based on specific features of the axons and terminals: two subtypes of type 1 axons and four subtypes of type 2 axons. The results revealed multiple modes of corticothalamic connectivity: sparsely distributed type 1 axons, dense plexuses of type 1 axons, type 2 axon terminal fields either singly or in clusters, and mixed plexuses of type 1 and type 2 axons. Only some cells in the plexuses were retrogradely labeled; some plexuses did not contain any labeled neurons, and many retrogradely labeled neurons were in the regions devoid of anterograde labeling. These connectivity patterns differed between thalamic nuclei. The results revealed much more complex relationships between M1 and thalamus than were previously thought to exist. It is suggested that this connectivity is neither of exclusively a feedback nature nor perfectly reciprocal but is subserved by a multitude of channels, most likely originating from different populations of cortical neurons, and feeding into a variety of functionally different neuronal networks, with each processing specific information.     

Comparison of neuronal activities in the monkey supplementary and precentral motor areas

Single cell activities were recorded from both the supplementary and precentral motor areas (SMA and PCM) of individual monkeys in order to compare their relation to performance. In the first series of experiments, monkeys were trained to perform a simple movement of key pressing in response to sensory signals of three different modalities: visual, auditory and somatosensory. It was found that the intensity of the movement associated neuronal activity was smaller in SMA than in PCM, and that onsets of neuronal activity in SMA were not as well correlated with the animal's movement onsets as those in PCM. These findings suggest that SMA is more remote from the peripheral motor apparatus than PCM. On the other hand, SMA seems to be closer to visual and auditory inputs. In the second series of experiments, monkeys were trained in a behavioural paradigm where instructions required them to predetermine their motor response to a signal of a particular sensory modality. In one situation, an instruction required the animal to be prepared to start a movement promptly in response to a forthcoming tone burst but to remain motionless if the signal was vibrotactile. In a second situation, a different instructional signal required the animal to be prepared to execute the movement if the vibrotactile, but not the tone burst, was presented. Striking differences in the instruction-induced activities in the two motor areas were found, indicating that SMA plays a more important role than PCM in a preparatory process leading to correct initiation on suppression of movement performance.     

Precentral cortical zones related to flexion and extension in two hindlimb movements in the monkey

Single units were recorded in the leg region of precentral cortex in two alert rhesus monkeys while each performed two separate leg movements, a pedaling movement involving both legs and an ankle flexion-extension movement by the leg contralateral to the cortex studied. Most units could be classed as +F or +E for each movement, depending on whether they were activated during the flexion (+F) or extension (+E) phase of movement. The electrode penetrations were spaced 1 mm apart in a grid pattern (30–40 tracks/monkey). When the locations of +F or +E units for each movement were plotted on the grid of penetrations, they appeared to be organized into large homogeneous zones of either +F or +E cells with surprisingly little overlap between zones. The zones for the two different movements were similar but not identical. Consistency from one movement to the other improved if the pattern of EMG activity during the two movements was taken into account. These data suggest that relatively complex muscle synergies may be represented in the precentral cortex.     

Temporal Coding of Amplitude and Frequency Modulation in the Rat Auditory Cortex

The rat primary auditory cortex was explored for neuronal responses to pure tones and sinusoidally amplitude-modulated (SAM) and frequency-modulated (SFM) stimuli. Units showed phase-locked responses to SAM stimulation (55%) and SFM stimulation (80%), with modulation frequencies up to 18 Hz. Tuning characteristics to the modulation frequency were mainly band-pass with best modulation frequencies (BMFs) between 4 and 15 Hz. Units with synchronized activity to SFM stimulation showed three response types with respect to the direction of the frequency modulation: 52% were selective to the upward direction, 30% to the downward direction, and 18% had no preference. Triangular frequency modulations were used to test if units were tuned to specific modulation frequencies or to specific rates of frequency change. In the vast majority of units tested the response characteristics were strongly influenced by varying the modulation frequency, whereas varying the rate of frequency change had little effect in the stimulus range used. Units that showed phase-locked responses to SAM and SFM stimulation had similar activity patterns in response to both types of stimuli. BMFs for SAM and SFM stimulation were significantly correlated. Intrinsic oscillations of up to 20 Hz could be seen in the spontaneous activity and after the stimuli independent of the stimulus type. Oscillation frequencies were significantly correlated with the BMFs of the respective units. The results are discussed in terms of a mechanism for periodicity detection based on a temporal code. This could be important for the recognition of complex acoustic signals.     

Central and peripheral control of the trigger mechanism for kicking and jumping in the locust

A crucial stage of the locust kick motor program is the trigger activity that inhibits the flexor motorneurons at the end of flexor-extensor coactivation and releases the tibia. One source of this inhibition is the M interneuron, which produces a spike burst at the time of the trigger activity. Previous work has suggested that sensory input resulting from extensor muscle tension may contribute to the M spike burst. We find that extensor muscle tension produced during thrusting behavior or by direct electrical stimulation with the tibia held fixed results in the depolarization of M, but this is not of sufficient amplitude to account for the M spike burst during the trigger activity. Furthermore, M still produces a spike burst after ablating the sensory systems that produce the response to the muscle stimulation. It is concluded that the major component of the M trigger activity is central in origin, although sensory feedback from extensor muscle tension makes some contribution. The combination of both central and peripheral paths for M activation may enhance the robustness of the behavior. J. Comp. Neurol. 404:212–220, 1999. © 1999 Wiley-Liss, Inc.     

Movement and non-movement related pallidal unit activity during bar press feeding behavior in the monkey

Activity was recorded from 358 neurons in the globus pallidus (GP) of monkeys (Macaca fuscata) during an operant feeding task consisting of 3 stages: (1) food or non-food presentation (1st stage); (2) bar pressing (2nd stage); and (3) food acquisition and ingestion (3rd stage). There were two kinds of neurons, one with high and the other with very low (almost silent), spontaneous firing rates. Two hundred and four neurons (57%) responded in one or more of the feeding stages. Of the 21 neurons which responded in the 1st stage, two responded selectively to food presentation, and 19 responded to both food and non-food visual presentation. One hundred and seventy-four neurons (49%) and 107 neurons (30%) responded in the 2nd and 3rd stages, respectively, and 106 (30%) of these were directly related to specific feeding motor acts such as arm extension, flexion, bar pressing, grasping, chewing etc. Both high and low firing neurons responded to motor acts with sharp or gradual onset. More than half of those that responded to arm extension showed laterality (contra or ipsi)- and function (extension or flexion)-dependent responses. The incidence of the motor related neurons was higher in the caudodorsal part of the GP. On the other hand, about one third, especially in the rostroventral part of the GP, showed dissociating responses in that they responded during bar pressing for food or during ingestion in an operant task, but not during bar pressing for non-food or during forcible ingestion. The magnitude of firing changes during arm extension and bar pressing depended on the nature of the food. Moreover, in trials using new food or false (model) food, firing changes during bar press appeared or disappeared within a few trials with no correlation to bar press movement. These data suggest heterogeneous functions within the GP; the caudodorsal part is strictly concerned with motor execution and preparation, while the rostroventral part is not related to motor function directly, but may rather be important in coupling internal, motivational information to the motor system.     

Long-lasting Potentiation of a Direct Central Connection between Identified Motor Neurons in the Locust

The plasticity of the direct central connection between the fast extensor and the posterior fast flexor tibiae motor neurons in the locust ( Schistocerca gregaria ) metathoracic ganglion was studied. An action potential in the fast extensor results in a monosynaptic excitatory postsynaptic potential (EPSP) in the flexor motor neuron. Antidromic stimulation of the fast extensor at 100 Hz for 3.5 s resulted in a long-lasting potentiation of the EPSP amplitude. The potentiation was not dependent on feedback caused by movement of the tibia, and was associated with an increase in the input resistance of the flexor motor neuron. The potentiation was heterosynaptic, and was not affected by bath application of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid. The potentiation was voltage dependent, as hyperpolarizing the flexor motor neuron during the stimulation blocked the development of the potentiation whereas depolarizing the flexor in the absence of presynaptic activity caused potentiation of subsequent fast extensor-evoked EPSPs. The depolarization-induced potentiation was calcium dependent. Antidromic stimulation of the fast extensor at 100 Hz for 3.5 s also caused modulation of the presynaptic action potential. The spike duration was increased and the amplitude of the afterhyperpolarization reduced. These effects were dependent on movement of the tibia. Bath application of the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin blocked the changes in the presynaptic spike. The modulation was probably due to the release of 5-HT from proprioceptive afferents that monitor movement of the tibia about the femur. The modulation of the presynaptic action potential increases transmitter release onto the flexor motor neurons, and this acts in synergy with the postsynaptic modulation to potentiate the connection.     

一种改良的胚胎大鼠颞叶海马区神经元的培养方法

目的:探索胚胎大鼠颞叶海马区神经元的改良培养方法。方法:在无血清培养基础上,采用改良的分离纯化法获取单细胞悬液,接种后在不同阶段通过加入不同配方的培养基进行培养,并进行免疫组化鉴定。结果:用该方法培养的颞叶海马区神经元细胞存活率高,生长状态良好,且βⅢ-tublin免疫染色为阳性,神经元细胞纯度可达90%以上。结论:改良分离、结合分阶段的不同培养条件是一种简单、高效的颞叶海马区神经元的纯化培养方法。     

Properties of delay-period neuronal activity in the primate prefrontal cortex during memory- and sensory-guided saccade tasks

The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term (or working) memory. Its cellular basis has been widely examined using the delayed-response paradigm in nonhuman primates. Sustained delay-period activity in DLPFC neurons with directional difference (i.e. directional delay-period activity) has been thought to represent visuospatial short-term (or working) memory. However, little is known about the activity of these neurons during a delay period when the sensory input remains. To address this issue, we examined neuronal activity in the DLPFC while macaque monkeys performed a memory-guided saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task required a memory-guided saccade for a remembered target location. The VGS task had the same temporal sequence as the MGS task, but the sensory stimulus remained during the delay period. We found that most of the DLPFC neurons with directional delay-period activity showed sustained activation during the 'delay' period in the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%). Neurons showing directional delay-period activity in the MGS task only ('M-neurons') were only 5% of the DLPFC neurons with directional delay-period activity. These findings indicate that most DLPFC neurons that are active during the delay period are also active when the sensory stimulus remains, suggesting that DLPFC neurons driven by mnemonic information are also driven by sensory input. Such sustained representation of information should have potential utility in flexible cognitive controls of behaviour.     

Craniofacial dysmorphogenesis in fetally irradiated nonhuman primates: implications for the neurodevelopmental hypothesis of schizophrenia.

BACKGROUND: Craniofacial abnormalities arising from gestational disturbances have been documented in some schizophrenic patients. Reduction of thalamic neurons, a key feature of the neuropathology of schizophrenia, could also have a prenatal origin via disruption of thalamic neurogenesis. This study investigates whether craniofacial dysmorphology and thalamic neuron loss might be associated manifestations of a disruption in embryonic development. METHODS: Thalamic neurons were deleted by exposing fetal macaques to x-rays during thalamic genesis (E33-42). Another group of macaques was irradiated after thalamic genesis (E70-81). Body, head, and facial measurements were obtained from the early irradiated (EX), late irradiated (LX), and control animals at adulthood. RESULTS: Head width, distance between outer eye edges, and ear width were smaller in EX macaques compared with control animals. The LX macaques exhibited only reduced ear width compared with control animals. CONCLUSIONS: These findings indicate that certain features of thalamic neuropathology and craniofacial dysmorphogenesis observed in schizophrenic patients may have a common etiology.     

Neurons in the amygdala of the monkey with responses selective for faces

To investigate the functions of the amygdala in visual information processing and in emotional and social responses, recordings were made from single neurons in the amygdala of the monkey. A population of neurons (40 of more than 1000 recorded in 4 monkeys) was investigated which responded primarily to faces. These neurons typically (1) responded to some human or monkey faces, which were presented to the monkey through a large aperture shutter so that response latencies could be measured, or were simply shown to the monkey, (2) responded to 2-dimensional representations of these faces, as well as to real 3-dimensional faces, (3) had no responses or only small (less than half maximum) responses to gratings, simple geometrical, other complex 3-D stimuli, or to arousing and aversive stimuli, (4) had response latencies of 110-200 ms, (5) were located in the basal accessory nucleus of the amygdala, (6) responded differently to different faces, as shown by measures of d', and could thus over a population of such neurons code information useful for making different responses to different individuals, (7) could in some cases (9/11 tested) respond to parts of faces, and (8) in a few cases (4/19 tested) responded more to a face which produced an emotional response. A comparison made in three monkeys of the responses of these neurons with the responses of 77 neurons with face-selective responses recorded in the cortex of the superior temporal sulcus (STS) showed that the amygdaloid neurons had longer response latencies (110-200 compared to 90-140 ms), and were in some respects more selective in their responses to different faces. It is suggested that the deficits in social and emotional behavior produced by amygdala lesions could be due in part to damage to a neuronal system specialized in utilizing information from faces so that appropriate social and emotional responses can be made to different individuals.     

Broadband Dynamics Rather than Frequency-Specific Rhythms Underlie Prediction Error in the Primate Auditory Cortex

Detection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography was conducted in three male monkeys, who passively listened to the auditory roving oddball stimuli. Local field potentials (LFPs) recorded over the auditory cortex underwent spectral principal component analysis, which decoupled broadband and rhythmic components of the LFP signal. We found that the broadband component captured the prediction error response, whereas none of the rhythmic components were associated with statistical irregularities of sounds. The broadband component displayed more stochastic, asymmetrical multifractal properties than the rhythmic components, which revealed more self-similar dynamics. We thus conclude that the prediction error response is captured by neuronal populations generating asynchronous broadband activity, defined by irregular dynamic states, which, unlike oscillatory rhythms, appear to enable the neural representation of auditory prediction error response.SIGNIFICANCE STATEMENT This study aimed to examine the contribution of oscillatory and asynchronous components of auditory local field potentials in the generation of prediction error responses to sensory irregularities, as this has not been directly addressed in the previous studies. Here, we show that mismatch negativity—an auditory prediction error response—is driven by the asynchronous broadband component of potentials recorded in the auditory cortex. This finding highlights the importance of nonoscillatory neural processes in the predictive monitoring of the environment. At a more general level, the study demonstrates that stochastic neural processes, which are often disregarded as neural noise, do have a functional role in the processing of sensory information.     

Opiate mechanism in reward-related neuronal responses during operant feeding behavior of the monkey

Reward-related neuronal activity and its modulation by morphine and naloxone was investigated by extracellular single neuron recording and electrophoretic application of drugs in the lateral hypothalamus, during operant feeding of the monkey. Morphine-sensitive neurons responded more often during bar press and ingestion-reward phases. Naloxone blocked only ingestion-reward responses, especially the inhibitory ones. The results suggest that the central opiate system can be involved in reward-related neuronal responses in the lateral hypothalamic area of the monkey.     

Dissociable substrates for body motion and physical experience in the human action observation network

Observation of human actions recruits a well-defined network of brain regions, yet the purpose of this action observation network (AON) remains under debate. Some authors contend that this network has developed to respond specifically to observation of human actions. Conversely, others suggest that this network responds in a similar manner to actions prompted by human and non-human cues, and that one's familiarity with the action is the critical factor that drives this network. Previous studies investigating human and non-human action cues often confound novelty and stimulus form. Here, we used a dance-learning paradigm to assess AON activity during observation of trained and untrained dance cues where a human model was present or absent. Results show that individual components of the AON respond differently to the human form and to dance training. The bilateral superior temporal cortex responds preferentially to videos with a human present, regardless of training experience. Conversely, the right ventral premotor cortex responds more strongly when observing sequences that had been trained, regardless of the presence of a human. Our findings suggest that the AON comprises separate and dissociable components for motor planning and observing other people's actions.     

Anatomical Evidence for Rod Input to the Parvocellular Pathway in the Visual System of the Primate

The question whether midget bipolar cells in macaque monkey retina receive input from rods was investigated using double-label immunocytochemistry. Flat midget bipolar cells (labelled with antibodies against recoverin) were found to be pre- and postsynaptic to All amacrine cells (labelled with antibodies against calretinin). These results support physiological evidence that rod photoreceptor signals could reach the parvocellular pathway at an early stage of visual processing.     

Cranial Motor Axons Respond Differently to the Floor Plate and Sensory Ganglia in Collagen Gel Co-cultures

Within the developing chick hindbrain, motor neurons differentiate in columns on either side of the ventral midline floor plate. Along the rostrocaudal axis, populations of motor neurons are organized segmentally with the trigeminal (V) and facial (VII) nuclei occupying successive pairs of rhombomeres. To reach their targets, motor axons follow stereotyped pathways. Branchiomotor and visceral motor axons of the Vth and VIIth nerves first project in a dorsal (lateral) direction away from the floor plate and towards the nerve exit point located in the alar plate of the even-numbered rhombomere of the pair. Having exited the hindbrain, axons grow in association with the cranial sensory ganglia before branchiomotor axons enter the branchial arches. We have investigated some of the factors that might guide cranial motor axons using a three-dimensional collagen gel culture system. When explants of hindbrain basal plate containing trigeminal or facial motor neurons were co-cultured with floor plate explants, axon outgrowth from the side facing the floor plate was inhibited in a manner consistent with chemorepulsion. When basal plate explants that contained an exit point were cultured alone, motor axons grew to the exit point and then stopped. When basal plate explants were co-cultured with trigeminal ganglia, motor outgrowth was increased in comparison with that in control cultures, suggesting a trophic influence. The findings presented here indicate that motor pathways are elaborated due to a progression of signals to which the growth cones respond in sequence.