The temporal structure of spike trains in the primate basal ganglia: afferent regulation of bursting demonstrated with precentral cerebral cortical ablation

We studied the temporal pattern of discharge of single units in the basal ganglia of awake primates sitting quietly. Bursting was studied with a procedure that identified individual bursts in a spike train, quantifying burst intensity (surprise), bursts per 1000 spikes, spikes per burst and burst length. Autocorrelation techniques were used to assess the dependencies of spike trains on the temporal order of intervals. Straital units had a greater tendency to burst (79% of units) than pallidal units (50%). The caudate nucleus and putamen had nearly identical burst properties on all measures. In the pallidum, bursting was more prevalent in the external segment and bursts were more intense and more frequent than in the internal segment. The autocorrelation analysis revealed that the temporal structure of the spike train was more dependent on the order of intervals in the striatum than in the pallidum. Bursting units had an increased probability of discharge after each spike and the relative refractory period was shorter in bursting units than units without bursts. Very few units exhibited cyclic discharge properties. Ablations of areas 4 and 6 in the precentral cortex demonstrated that striatal bursting was under afferent control. The putamen, which receives more cortical afferents from areas 4 and 6 than the caudate nucleus, had fewer and less intense bursts after the afferents were lesioned. Bursts intensity did not change in the pallidum after the lesion. The findings indicate that bursting properties contribute to discharge variability in the basal ganglia and suggest that information transfer in the striatum may utilize bursts. In contrast, rate coding may be a more important mechanism for units in the pallidum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29420/1/0000496.pd

Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's

BACKGROUND: Excessive sequential stereotypy of behavioral patterns (sequential super-stereotypy) in Tourette's syndrome and obsessive compulsive disorder (OCD) is thought to involve dysfunction in nigrostriatal dopamine systems. In sequential super-stereotypy, patients become trapped in overly rigid sequential patterns of action, language, or thought. Some instinctive behavioral patterns of animals, such as the syntactic grooming chain pattern of rodents, have sufficiently complex and stereotyped serial structure to detect potential production of overly-rigid sequential patterns. A syntactic grooming chain is a fixed action pattern that serially links up to 25 grooming movements into 4 predictable phases that follow 1 syntactic rule. New mutant mouse models allow gene-based manipulation of brain function relevant to sequential patterns, but no current animal model of spontaneous OCD-like behaviors has so far been reported to exhibit sequential super-stereotypy in the sense of a whole complex serial pattern that becomes stronger and excessively rigid. Here we used a hyper-dopaminergic mutant mouse to examine whether an OCD-like behavioral sequence in animals shows sequential super-stereotypy. Knockdown mutation of the dopamine transporter gene (DAT) causes extracellular dopamine levels in the neostriatum of these adult mutant mice to rise to 170% of wild-type control levels. RESULTS: We found that the serial pattern of this instinctive behavioral sequence becomes strengthened as an entire entity in hyper-dopaminergic mutants, and more resistant to interruption. Hyper-dopaminergic mutant mice have stronger and more rigid syntactic grooming chain patterns than wild-type control mice. Mutants showed sequential super-stereotypy in the sense of having more stereotyped and predictable syntactic grooming sequences, and were also more likely to resist disruption of the pattern en route, by returning after a disruption to complete the pattern from the appropriate point in the sequence. By contrast, wild-type mice exhibited weaker forms of the fixed action pattern, and often failed to complete the full sequence. CONCLUSIONS: Sequential super-stereotypy occurs in the complex fixed action patterns of hyper-dopaminergic mutant mice. Elucidation of the basis for sequential super-stereotypy of instinctive behavior in DAT knockdown mutant mice may offer insights into neural mechanisms of overly-rigid sequences of action or thought in human patients with disorders such as Tourette's or OCD

A microdrive positioning adapter for chronic single unit recording

A new micropositioner design for use in chronic, transdural single unit recording studies is presented. The adapter is used to position an electrode microdrive assembly to any desired location within a surgically implanted recording chamber. The adapter uses a radial positioning technique that requires few moving parts. In comparison with the X-Y slide manipulator it replaces, it is more durable, it provides access to a larger brain area, and it attaches more securely. In addition, provision can be made to mount a second microdrive, permitting two electrodes to be manipulated independently.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27594/1/0000638.pd

A multiwire microelectrode for single unit recording in deep brain structures

A method is described by which a single shaft multiwire microelectrode can be fabricated efficiently. The resulting electrode can be attached to a commercial microdrive and used for single neuronal unit recording from one or more tracks in deep brain structures of anesthetized or awake animals. The electrode consists of a 30 gauge stainless steel cannula through which multiple strands of 13 [mu]m insulated tungsten microwires are threaded. At the electrode tip the wires protude 3-4 mm from the cannula and are cut individually at suitable offsets. The tip is stabilized and fixed to the cannula with cyanoacrylate. At the base of the electrode the wires are threaded through flexible plastic tubing that provides strain relief and are glued to individual pins of a miniature connector that plugs into a field effect transistor (FET) voltage follower. Good single unit recordings have been obtained routinely from the basal ganglia of awake, behaving monkeys with this electrode.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28587/1/0000395.pd

Primate basal ganglia activity in a precued reaching task: preparation for movement

Single cell activity was recorded from the primate putamen, caudate nucleus, and globus pallidus during a precued reaching movement task. Two monkeys were trained to touch one of several target knobs mounted in front of them after an LED was lighted on the correct target. A precue was presented prior to this target “go cue” by a randomly varied delay interval, giving the animals partial or complete advance information about the target for the movement task. The purpose of this design was to examine neuronal activity in the major structures of the basal ganglia during the preparation phase of limb movements when varying amounts of advance information were provided to the animals. The reaction times were shortest with complete precues, intermediate with partial precues, and longest with precues containing no information, demonstrating that the animals used precue information to prepare partly or completely for the reaching movement before the target go cue was given. Changes in activity were seen in the basal ganglia during the preparatory period in 30% of neurons in putamen, 31% in caudate nucleus, and 27% in globus pallidus. Preparatory changes were stronger and more closely linked to the time of movement initiation in putamen than in caudate nucleus. Although the amount of information contained in the precues had no significant effect on preparatory activity preceding the target go cue, a directional selectivity during this period was observed for a subset of neurons with preparatory changes (15% in putamen, 11% in caudate nucleus, 14% in globus pallidus) when the precue contained information about the upcoming direction of movement. A smaller subset of neurons showed selectivity for the preparation of movement amplitude. A larger number of preparatory changes showed selectivity for the direction or amplitude of movement following the target go cue than in the delay period before the cue. The intensity of preparatory changes in activity in many cases depended on the length of the delay interval preceding the target go cue. Even following the target go cue, the intensity of the preparatory changes in activity continued to be significantly influenced by the length of the preceding delay interval for 11% of changes in putamen, 8% in caudate nucleus, and 18% in globus pallidus. This finding suggests that preparatory activity in the basal ganglia takes part in a process termed motor readiness. Behaviorally, this process was seen as a shortening of reaction time regardless of precue information for trials in which the delay interval was long and the animals showed an increased readiness to move. Preparatory activity in putamen following the target go cue was most intense in trials with a short delay interval, in which motor readiness had not achieved its maximum level prior to the go cue. The results of this study indicate that the basal ganglia are involved in multiple aspects of preparatory processing for limb movement. Preparatory processing is therefore unlikely to be divided anatomically along the functional lines examined in this study. In the basal ganglia, preparatory processing reflects both preparation for target selection and control of timing the onset of movement (motor readiness). These characteristics can be integrated in a functional scheme in which the basal ganglia are predominantly responsible for the automated execution of well-trained behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46566/1/221_2004_Article_BF00229653.pd

Unilateral striatal lesions in the cat disrupt well-learned motor plans in a GO/NO-GO reaching task

 We examined the changes in learned and spontaneous motor behavior after a unilateral excitotoxin lesion of the neostriatum. Cats were trained to perform a sensory-cued GO/NO-GO reaching task. Success rate, reaction time, movement speed and kinematic patterns were used to characterize motor system properties. In addition, motor properties before and after the lesion were compared by clinical neurological examinations and video tape observations of free-range behavior. We found that in normal animals motor performance in the task was fluent, highly automatic and skillful with consistent patterns from trial to trial and day to day. The striatal lesion resulted in a marked impairment in the animals’ ability to perform the automatic response to the sensory cues in the motor task. In contrast, sensorimotor behavior in contexts apart from the task was altered minimally, with changes that were often difficult to detect. The animals recovered their ability to perform the task gradually, although they never reached prelesion performance levels in up to 24 weeks of evaluation. The animals had difficulty making reaching movements in GO trials and, in NO-GO trials failures to withhold movements were more frequent. Failures were due to a specific inability to execute previously well-learned movements in response to cues and not to an inability to recognize and interpret the cues. The lesion effects were restricted to the automatic motor response to the learned cues, as the animals could make reaching movements to the target without obvious impairment in response to novel stimuli. They also made similar spontaneous movements apart from the motor task that appeared to be unimpaired. The unique motor style and strategies that characterized the behavior of individual animals prior to the lesion were still evident after the lesion, even though they were superimposed on lower success rates and slower movement speeds. Our findings suggest that the basal ganglia facilitate the fluent and rapid execution of sequences of well-learned sensorimotor behavior, but the representations of motor plans are not stored in the basal ganglia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42008/1/221-113-3-379_71130379.pd

A signal generator for testing extracellular recording amplifiers and probes

A portable signal generator that simulates the amplitude and frequency of neuronal signals for testing extracellular recording amplifiers is described. The signal generator is easy to construct and it is extremely useful in tracing signal processing stages in neurophysiological equipment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27130/1/0000123.pd

Altered locus coeruleus–norepinephrine function following single prolonged stress

Data from preclinical and clinical studies have implicated the norepinephrine system in the development and maintenance of post‐traumatic stress disorder. The primary source of norepinephrine in the forebrain is the locus coeruleus ( LC ); however, LC activity cannot be directly measured in humans, and previous research has often relied upon peripheral measures of norepinephrine to infer changes in central LC –norepinephrine function. To directly assess LC –norepinephrine function, we measured single‐unit activity of LC neurons in a validated rat model of post‐traumatic stress disorder – single prolonged stress ( SPS ). We also examined tyrosine hydroxylase mRNA levels in the LC of SPS and control rats as an index of norepinephrine utilisation. For electrophysiological recordings, 92 LC neurons were identified from 19 rats ( SPS , 12; control, 7), and spontaneous and evoked responses to a noxious event (paw compression) were recorded. Baseline and restraint stress‐evoked tyrosine hydroxylase mRNA expression levels were measured in SPS and control rats ( n  = 16 per group) in a separate experiment. SPS rats showed lower spontaneous activity but higher evoked responses, leading to an enhanced signal‐to‐noise ratio of LC neurons, accompanied by impaired recovery from post‐stimulus inhibition. In concert, tyrosine hydroxylase mRNA expression in the LC of SPS rats tended to be lower at baseline, but was exaggerated following restraint stress. These data demonstrate persistent changes in LC function following stress/trauma in a rat model of post‐traumatic stress, as measured by differences in both the electrophysiological properties of LC neurons and tyrosine hydroxylase mRNA transcription. Single unit activity of LC neurons and TH mRNA levels were measured in the S ingle P rolonged S tress model of P ost‐traumatic stress disorder. SPS decreased rates of spontaneous discharge, exaggerated phasic responses of LC neurons and augmented stress‐enhanced TH mRNA expression. These data demonstrate sustained LC ‐ NE system abnormalities in SPS , providing an opportunity to study the interaction between LC ‐ NE system, and other PTSD ‐like physiological and behavioral changes seen in this model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97273/1/ejn12095.pd

Enhancing high-speed digitization of single-unit neuronal activity on a microcomputer using a hybrid software-hardware technique

A new data acquisition technique allows a microcomputer simultaneously to digitize spikes at high rates, analyze spike waveforms for computer-based spike separation and manage other control tasks. The technique has two key features: a software scheduling routine written in a high-level language and a hardware analog delay of neuronal signals using simple hardware external to the computer. The technique provides an alternative for real-time data acquisition and can be used on microcomputers without requiring interrupt processing and assembly language programming.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27911/1/0000332.pd

Effects of excitotoxic striatal lesions on single unit activity in globus pallidus and entopeduncular nucleus of the cat

Striatal projections to the globus pallidus and entopeduncular nucleus are thought to be GABAergic and inhibitory. Thus, striatal lesions might be expected to increase the spontaneous discharge rate of neurons in these nuclei. To test this prediction, we recorded spontaneous single unit activity from awake cats sitting quietly before and 7-160 days after striatal lesions. Striatal lesions were produced by injecting ibotenic acid into the caudate nucleus and putamen. Median, standard deviation, mean, and coefficient of variation of the interspike intervals were calculated for each unit. In globus pallidus the striatal lesion resulted in a significant decrease in median interval length, i.e. an increase in the discharge rate. The prelesion median of 36 ms (S.E.M. = 2.3) decreased 11% to a postlesion value of 32 ms (S.E.M. = 2.1.). The lesion also resulted in a significant decrease in the variability of interspike intervals. The coefficient of variation, 1.31 (S.E.M. = 0.08) before the lesion, decreased 25% to 0.97 (S.E.M. = 0.06) after the lesion. In entopeduncular nucleus, the lesion had no statistically significant effect on the rate of activity, but a significant decrease in the variability of activity occurred. The median interval was 33 ms (S.E.M. = 3.3) before the lesion and decreased 2% to 32 ms (S.E.M. = 2.4). The coefficient of variation decreased 48% from 1.44 (S.E.M. = 0.1) to 0.73 (S.E.M. = 0.03). These observations support the hypothesis that loss of GABAergic inputs to the globus pallidus results in disinhibition. The discharge rate in entopeduncular nucleus was not affected by the striatal lesion, suggesting that striatal substance P or subthalamic excitatory inputs may have a role in regulating discharge rate in the entopeduncular nucleus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27691/1/0000075.pd