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B I Hyland

Publications and source records attributed to B I Hyland.

13 recordsLinked to original sources

Firing modes of midbrain dopamine cells in the freely moving rat.

There is a large body of data on the firing properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the firing properties of these cells in freely moving rats. We examined this by recording from the midbrain dopamine cell fields using chronically implanted microwire electrodes. (1) In most cases, slowly firing cells with broad action potentials were profoundly inhibited by the dopamine agonist apomorphine, consistent with previously accepted criteria. However, a small group of cells was found that were difficult to classify because of ambiguous combinations of properties. (2) Presumed dopamine cells could be divided into low and high bursting (>40% of their spikes in bursts) groups, with the majority having low bursting rates. The distribution of burst incidence was similar to that previously reported with chloral hydrate anaesthesia, but the average intraburst frequency was higher in the conscious animal at rest and was higher again in bursts triggered by salient stimuli. (3) There was no evidence for spike frequency adaptation within bursts on average, consistent with the hypothesis that afterhyperpolarisation currents may be disabled during behaviourally induced bursting. (4) Presumed dopamine cells responded to reward-related stimuli with increased bursting rates and significantly higher intraburst frequencies compared to bursts emitted outside task context, indicating that modulation of afferent activity might not only trigger bursting, but may also regulate burst intensity. (5) In addition to the irregular single spike and bursting modes we found that extremely regular (clock-like) firing, previously only described for dopamine cells in reduced preparations, can also be expressed in the freely moving animal. (6) Cross-correlation analysis of activity recorded from simultaneously recorded neurones revealed coordinated activity in a quarter of dopamine cell pairs consistent with at least "functional" connectivity. On the other hand, most dopamine cell pairs showed no correlation, leaving open the possibility of functional sub-groupings within the dopamine cell fields. Taken together, the data suggest that the basic firing modes described for dopamine cells in reduced or anaesthetised preparations do reflect natural patterns of activity for these neurones, but also that the details of this activity are dependent upon modulation of afferent inputs by behavioural stimuli.

Action Potentials↗

A cellular mechanism of reward-related learning.

Positive reinforcement helps to control the acquisition of learned behaviours. Here we report a cellular mechanism in the brain that may underlie the behavioural effects of positive reinforcement. We used intracranial self-stimulation (ICSS) as a model of reinforcement learning, in which each rat learns to press a lever that applies reinforcing electrical stimulation to its own substantia nigra. The outputs from neurons of the substantia nigra terminate on neurons in the striatum in close proximity to inputs from the cerebral cortex on the same striatal neurons. We measured the effect of substantia nigra stimulation on these inputs from the cortex to striatal neurons and also on how quickly the rats learned to press the lever. We found that stimulation of the substantia nigra (with the optimal parameters for lever-pressing behaviour) induced potentiation of synapses between the cortex and the striatum, which required activation of dopamine receptors. The degree of potentiation within ten minutes of the ICSS trains was correlated with the time taken by the rats to learn ICSS behaviour. We propose that stimulation of the substantia nigra when the lever is pressed induces a similar potentiation of cortical inputs to the striatum, positively reinforcing the learning of the behaviour by the rats.

Animals↗

Parameter precuing and motor preparation.

A movement task was used to investigate the effects of precued variables on reaction time. The task involved rapid rotation of a hand-held manipulandum to target locations and required either pronation or supination of the forearm through short or long extent. The effects on reaction time of precues signalling target direction, extent, or a combination of direction and extent, were measured. The longest reaction times occurred when no information about direction or extent was provided in the precue (all parameters uncertain). Complete prior specification of target position produced the shortest reaction times. Specification of direction when extent was uncertain produced a significantly larger reduction in reaction time than specification of extent when direction was uncertain. Prior specification of extent also produced a small but significant reduction in reaction time relative to the condition in which direction and extent were specified in a mutually conditional manner. The results are discussed in relation to parameter precuing and motor programming, in which the direction is programmed by the pre-selection of neurons representing the muscles to be used in the task while programming of extent is represented by their level of activity during task performance.

Acoustic Stimulation↗

Foreperiod length, but not memory, affects human reaction time in a precued, delayed response.

The effect of foreperiod length on reaction time in memorized (MM) and nonmemorized (NM), precued, delayed responses was investigated. Six subjects participated in one long and one short foreperiod schedule testing session. An aiming task, using elbow supination/pronation, in response to a visual stimulus was employed. In the MM condition, target spatial information was available for a fraction of the foreperiod duration. In the NM condition, target information was available continuously until the subject attained the target position. Subjects responded with a significantly longer latency in the long foreperiod schedule. Within each foreperiod schedule, the shortest foreperiod resulted in significantly longer reaction time. However, the absolute value of foreperiod did not have a major effect on reaction time latency. Memorization and nonmemorization conditions did not affect reaction time.

Adult↗

Muscle activity during forelimb reaching movements in rats.

The absolute timing, and correlation in time of activity in a number of shoulder, elbow and wrist muscles in the rat was analysed in relation to onset and termination of the extension phase of a skilled forelimb reaching movement. Movement onsets were analysed separately in the component upward, forward and medial directions. On average, movements in the upward and medial directions occurred together, prior to forward movement. Latissimus dorsi activity was the earliest muscle event, occurring approximately 150 ms prior to movement, whilst onset of teres major activity, possibly related to paw elevation, had the highest temporal correlation with movement onset. Triceps activity was strongly time locked to the end of the reach, and may have provided final extensor thrust to complete the reaching movement. Although it is possible to speculate on possible roles of particular EMG bursts, multiple (often anatomically antagonistic) muscles were active at all stages of the reach, and no unique muscle relationships to initiation of individual movement components could be identified. It is concluded that reaching movements are produced by temporal variation in distributed activity among all available muscles.

Animals↗

Responses in the diagonal band of Broca, adjacent septal nuclei and the islands of Calleja of cats to stimulation of the subcallosal fornix, medial basal hypothalamus and medial forebrain bundle.

The projection of neurons in the septal nuclei and the insula magna of the islands of Callaja (IC) was explored together with their response to stimulation of the fornix. The septal nuclei all contained neurons projecting in the medial forebrain bundle (MFB). Only the diagonal band of Broca (DBB) and the lateral septal nucleus (LS) contained many neurons projecting toward the medial basal hypothalamus (MBH). The spatial distribution of neurons excited by stimulation of the fornix in the DBB was almost identical with the distribution of neurons projecting toward the MBH and there was considerable overlap (10/28 cells). In the medial septal nucleus the spatial distribution of neurons excited by stimulation of the fornix and neurons projecting in the MFB was similar and there was considerable overlap (6/21 cells). The connectivity of the IC resembled that of the MS but there was little overlap between the neurons excited by fornix stimulation and those projecting in the MFB (1/27 cells). In the LS there were almost equal numbers of neurons projecting in the MFB and toward the MBH but there was very little input from the fornix. Neurons were significantly more often excited by stimulation of the lateral fornix, carrying axons from the subiculum, than they were by medial stimulation exciting axons from Ammon's horn. Axons projecting toward the MBH or in the MFB had conduction velocities less than 1 m/s.

Animals↗

Stimulation of the LH release by naloxone in anaesthetized cats after ovariectomy.

The effect of intravenous injections or infusions of the opioid receptor antagonist naloxone on the secretion of luteinizing hormone (LH) was studied in 18 spayed cats anaesthetized with Althesin. Effective injections significantly increased the LH concentration of plasma samples (taken every 10-15 min and measured by radio-immunoassay) to a peak 20-30 min after injection. The concentration thereafter declined exponentially (ke = 0.42), and, in 4/8 trials rose again significantly and declined again without further injection. The threshold dose was between 0.4 and 0.5 mg/kg. There did not appear to be a dose dependence of the effect above threshold. Infusion of naloxone at levels up to 5 mg/kg/h was effective in producing a pulsatile release of LH and repeated injections of threshold doses (0.5 mg/kg) could produce a maintained plateau and pulsatile release at frequencies comparable to pulse frequencies in vivo.

Anesthesia↗

Luteinizing hormone release in the anesthetized cat following stimulation in the diagonal band of Broca, dorsal septum and fornix.

The release of luteinizing hormone (LH) in response to electrical stimulation of septal nuclei (the diagonal band of Broca, DBB, and dorsal septal nucleus) and the subcallosal fornix has been studied in gonadectomized female cats. The cats were anesthetized with Althesin. Electrodes were placed on the medial and lateral aspects of the subcallosal fornix and paired bipolar stimulating electrodes were aimed at the DBB or dorsal septal nucleus. The effect of electrical stimulation of these regions on the secretion of LH was studied by radioimmunoassay of LH in serial blood samples taken before, during and after stimulation. Stimulation in the DBB or in the dorsal septal nucleus resulted in a peak of LH release during stimulation followed by further spontaneous peaks. All peaks showed an exponential decline. The frequency of spontaneous peaks following stimulation could reach the level found in unanesthetized cats. Stimulation of the subcallosal fornix produced a significant depression in the amplitude of LH release. The effects of DBB, dorsal septal and fornix stimulation are all exerted, we suggest, by projections to LHRH containing neurons in the preoptic region.

Alfaxalone Alfadolone Mixture↗

Distribution and projection of single units in the cat preoptic region responding to stimulation of the medial amygdala.

Neuronal responses were recorded extracellularly in the preoptic region of 11 male castrate cats following stimulation in the 'medial' group of amygdalar nuclei (medial, basomedial, basolateral). The latency of responses varied with the site of stimulation and could be explained if connections to the preoptic region were made through both the stria terminalis and the ventral amygdalofugal pathway. Projection of 13% of orthodromically excited preoptic units to the medial basal hypothalamus was established by collision tests following stimulation in these regions. The amygdalar excitation was probably exerted through the amygdalofugal pathway. In 5/6 cats the amygdalar stimulation was successfully used to raise plasma LH levels. In one cat no preoptic units projecting to the medial basal hypothalamus were found and in the cat which failed to increase plasma LH in response to amygdala stimulation, 5 such units were found. We conclude the pathway from the amygdala through the preoptic region to the hypothalamus may not be the way in which amygdalar stimulation affects LH release in the cat. Projection of 10% of orthodromically excited preoptic units in the medial forebrain bundle was established by collision tests in 3 cats. These identified units were driven from amygdalar sites thought to project to the preoptic region by ventral amygdalofugal pathways.

Amygdala↗

Responses of cat preoptic neurons to stimulation of the medial frontal cortex and the medial basal hypothalamus.

Responses of single preoptic neurons to electrical stimulation of the medial frontal cortex, the mediobasal hypothalamus (MBH) and the medial forebrain bundle (MFB) were recorded in anaesthetised cats. Single pulse stimulation of the medial frontal cortex orthodromically drove 96 otherwise quiescent preoptic neurons, which were found more frequently in the dorsal preoptic region, inhibited 53% of the spontaneously active preoptic neurons and excited 16%. Testing of cortically influenced preoptic neurons with MBH or MFB stimulation resulted in antidromic invasion of 6% (MBH) and 9% (MFB). Convergence of orthodromic inputs from medial frontal cortex and MBH was detected in 78% of spontaneously active preoptic neurons, and three-way convergence including input from MFB was noted in 17% of neurons tested with all stimulators. Some cortex-response neurons were found to also respond to vaginal or anal probing, paw squeezing and haemorrhage. The role of this input to the preoptic region from medial frontal cortex remains to be elucidated, but may include neuroendocrine, behavioural and homeostatic functions.

Animals↗

Electrophysiological evidence for a projection from medial prefrontal and anterior limbic cortex toward the medial preoptic area in the cat.

Neurons in cat medial prefrontal cortex, anterior limbic cortex and possibly the indusium griseum were identified by antidromic invasion as having axonal projections towards the medial preoptic region, using both macro- and microstimulation techniques. These projecting axons were found to be of slow conduction velocity (0.2-4.8 m/s) and to in some cases also send branches towards the anteromedial thalamus, mediodorsal thalamus, ventromedial tegmentum, basolateral amygdala or medial forebrain bundle. Threshold-depth curves for axons excited by microstimulation in the medial preoptic region were very steep, with proportionality constants of 0.3-7.1 micron/microA. Calculations based on the threshold-depth curves confirmed that microstimulation was most probably only activating axons within the MPO, and current spread to lateral fibers of passage following macrostimulation in the MPO was not detected in the branching studies.

Animals↗

Does the precommissural fornix excite neurons in the cat dorsal septum which project to the medial preoptic region?

The possibility that effects of fornix stimulation on units in the medial preoptic region (MPO) may be via an interposed neuron in the dorsal septum was investigated using electrophysiological techniques. We found a reciprocal monosynaptic linkage between the MPO and the dorsal, medial and fimbrial septal nuclei. When recording in the MPO, stimulation of the dorsal septum affected 59% of spontaneously active units. Of all MPO units synaptically excited by stimulation of the dorsal septum 33% also had an input from the fornix. When recording in the dorsal septum during stimulation of the MPO and fornix, units synaptically driven by, or antidromically invaded following MPO stimulation, were found in caudal regions of the DS and units excited by stimulation of the fornix were located in more rostral regions. Units excited by stimulation of the fornix were never antidromically invaded following stimulation in the MPO, so there was no direct pathway for fornix excitation in the dorsal septum to reach the MPO.

Action Potentials↗

Luteinizing hormone release in the anaesthetised cat following electrical stimulation of limbic structures.

The release of luteinizing hormone (LH) in response to electrical stimulation of limbic centres, namely the medial preoptic region (MPO) medial basal hypothalamus (MBH) and the medial amygdala (AME) has been studied in the anaesthetised gonadectomized cat. Chronically gonadectomized cats were anaesthetised with pentobarbitone or Althesin and paired bipolar stimulating electrodes were aimed at the MPO, AME or MBH. The effect of electrical stimulation of these regions on the secretion of LH was studied by radio-immunoassay of LH in serial blood samples taken before, during and after stimulation. No change in plasma LH in response to electrical stimulation was ever recorded during pentobarbitone anaesthesia. During Althesin anaesthesia stimulation in the MPO more often than not resulted in a peak of LH release during stimulation. A peak release of LH during stimulation was also recorded when electrodes were placed in the arcuate-median eminence region of the MBH. The time-course of these peaks in LH secretion was similar to the time-course of the plasma LH responses recorded following a single intravenous injection of gonadotrophin-releasing hormone (GnRH). In contrast, electrodes placed in AME had no effect on plasma LH during electrical stimulation, but immediately after stopping it, a small LH peak was recorded. The time-course of these responses suggests a pulse release of GnRH, the rapid response to MPO and MBH stimulation possibly being the result of a direct action on GnRH neurons while the delayed AME response may be produced by AME projections to the GnRH release system. These responses could be likened to the surge of LH which in the cat occurs post-coitus.

Amygdala↗