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Biomedical subjects

J I Hubbard

Publications and source records attributed to J I Hubbard.

At least 37 records · Page 2Linked to original sources
PubMed1987

The influence of the estrous cycle, persistent estrus, ovariectomy and estrogen replacement, on the numbers and frequency of spontaneously active neurons in slices of the rat preoptic region in vitro.

Spontaneous single-unit activity was studied in the preoptic region of rat brain slices. Similar unit frequencies were recorded during the estrous cycle and for all ovariectomized (OVX) rats (median frequencies between 0.8 and 2.0 Hz). Higher frequencies were recorded in persistent estrus (PE) (median 3.5 Hz) and in males (median 3.4 Hz), P vs estrus less than 0.001. The mean percentage of tracks with units was low at estrus (15%), at diestrus (18%), in OVX rats (16%) and male rats (22%), and was significantly increased in metestrus (36%) and proestrus (33%) (P vs estrus less than 0.01) and in OVX rats after estrogen treatment (P less than 0.05 to P less than 0.01). It is suggested that the increased number of units found in OVX rats after estrogen treatment and in PE rats are both effects of prolonged elevated levels of estrogen in the brain.

Action Potentials↗
PubMed1987

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↗
PubMed1987

Neuron responses to substance P and enkephalin in rat dorso-lateral septum in vitro.

Using an in vitro brain slice technique the responses of spontaneously active neurons in the rat dorso-lateral septum to 10 nM substance P (SP) and enkephalin were determined. Fewer neurons responded to SP (41%) than to enkephalin (55%). The SP responses were 13 excitations, 14 inhibitions, the enkephalin responses were 13 excitations, 14 inhibitions and 11 responded to both, 6 of these were inhibited by both. Immunocytochemical techniques have shown there is a discrete localisation of SP and enkephalin axons and terminals in the rat septum. SP responsive neurons were associated with the SP terminal-rich region (p = 0.01) but no association was found for enkephalin responses in the enkephalin terminal-rich region (p = 0.7).

Action Potentials↗
PubMed1986

Neurotensin excites neurons in the arcuate nucleus of the rat hypothalamus in vitro.

The effects of neurotensin (NT) on 41 spontaneously active neurons in the rat hypothalamic arcuate nucleus (ARC) were determined using an in vitro brain slice technique. Addition of NT (1 microM to 10 nM) to the perifusing medium allowed the action of known concentrations of NT to be examined. Concentrations of peptide greater than 10 nM evoked excessive depolarization of sensitive neurons resulting in long periods of postexcitatory inhibition. At 10 nM, NT evoked reversible and repeatable excitatory (20%) and inhibitory (25%) responses. When synaptic activity was blocked by lowering the Ca2+ and raising the Mg2+ concentration of the medium only excitatory responses (25% of units tested) were observed. These results demonstrate a potent excitatory action of NT within the hypothalamic ARC at the single cell level.

Action Potentials↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

Distribution of osmosensitive cells in the preoptic and adjacent regions of cat brains.

The response of neurons in the preoptic and adjacent regions of the brain to intracarotid injection of hyperosmotic solutions was studied in 22 anesthetized cats. NaCl (0.5 M) caused a brisk acceleration of frequency lasting over 100 s in 120 of 207 units (58%). Glucose (2 M) and sucrose (2 M) had similar but smaller effects, and urea (2 M) was ineffective. Responding units were found in all parts of the preoptic region, the diagonal band of Broca (vertical limb), the lateral septal nucleus, nucleus accumbens and anterior hypothalamus.

Animals↗
PubMed1985

Inhibitory action of adrenocorticotrophin on rat arcuate neurons in vitro.

Extracellular recordings were made from 52 units in perifused 300 microns thick slices of rat hypothalamus taken parallel to the ventricular surface of the arcuate nucleus and kept at 37 degrees C in an organ bath. Addition of 8 nM adrenocorticotrophic hormone (ACTH) to the perfusate reversibly and rapidly inhibited 15 of the 38 units found within 300 microns of the ventricular surface (in the arcuate nucleus), and there were no comparable excitations. A prompt and reversible excitation of 6/14 units by ACTH was found when records were made from units found 300-600 microns lateral to the ventricle in the lateral arcuate region. It is suggested that ACTH may be an inhibitory transmitter in the arcuate nucleus and that this action may be an inhibition of ACTH-containing neurons.

Action Potentials↗
PubMed1985

Characterization of fimbria input to nucleus accumbens.

The hippocampal input to the nucleus accumbens was studied by correlative electrophysiological and anatomical techniques in acutely prepared rabbits. Field and extracellular unitary potentials were recorded in the nucleus accumbens following ipsilateral fimbria stimulation. Analysis of the components of the field response was based on the relevant correlations with extracellular unitary activity. The cellular types that are the recipients of the hippocampal projection were determined by combined intracellular horseradish peroxidase (HRP) and Golgi analyses. The distribution of the hippocampal input was determined by combined field potential and current source density analyses. It was found that the ipsilateral fimbria projection was distributed to the dorsal two-thirds of the nucleus, with the projection being heaviest in the more caudal portions of the nucleus. The negative (N) component of the field response was studied by correlating its behavior with the appropriate extracellular unitary recordings. It was concluded that the N-component represented an envelope of monosynaptically activated action potentials. The positive (P) component of the field response throughout the nucleus accumbens was studied pharmacologically with the iontophoretic administration of bicuculline. The P-components, in both the dorsal and ventral regions of the nucleus, were diminished by bicuculline application, indicating that this potential results from the activation of gamma-aminobutyric acid (GABA) mechanisms. The cell populations that are the targets for the hippocampal projections were studied by the technique of intracellular staining with HRP. These results were correlated with the findings of a Golgi analysis. Two distinct cell types were found to respond in a monosynaptic manner to ipsilateral fimbria stimulation. The most common of the two were the small-to medium-sized spiny neurons, and they were distributed throughout the nucleus. These cells have a spherical dendritic arrangement. The second, and most distinctive, of the cell types were the large aspiny neurons. These cells were distributed medially and caudally in the nucleus. Two of the outstanding features of these cells were the expanse of their dendritic domains and the fact that axons originated from relatively remote portions of the dendrites.

Animals↗
PubMed1984

LH-RH in picomole concentrations evokes excitation and inhibition of rat arcuate neurones in vitro.

A medial sagittal brain slice was developed, which enabled electrophysiological recording from spontaneously active neurones adjacent to the infundibular recess of the rat arcuate nucleus. Luteinizing hormone-releasing hormone (LH-RH) (10 nM-10 pM) significantly altered the frequency of 21 out of 31 units tested, exciting 14 and inhibiting 7 others. The excitatory responses were often not maintained during the exposure to LH-RH but either returned to pre-exposure frequency or displayed an inhibition of discharge. A neural model incorporating recurrent inhibition of LH-RH-excited neurones is proposed to explain these responses, thought to be endogenously evoked by collateral innervation of the arcuate nucleus by medial preoptic neurones projecting to the median eminence.

Animals↗
PubMed1984

Rat organum vasculosum laminae terminalis in vitro: responses to transmitters.

Spontaneous single-action potentials (units) were recorded extracellularly from explants of the rat organum vasculosum laminae terminalis in vitro. Increasing the osmotic pressure of the bathing solution by 15% by adding NaCl or mannitol increased frequency, whereas reducing the osmotic pressure by 15% by omitting NaCl reduced frequency. The mean frequency ratio (test/control) for 6 (of 13) units responding to a 15% increase was 2.2 +/- 0.5 (SE), and for 8 (of 11) units responding to a 15% decrease it was 0.6 +/- 0.1. These responding units all lay within 55 microns of the ventricular surface. Reduction of the calcium concentration from 2 to 0.75 mmol X l-1 increased the mean frequency of units by 55%. Putative transmitters were added to the bathing solution at 0.1 mol X l-1. The results were as follows: carbamylcholine (26 units), 27% excited and 19% inhibited; luteinizing hormone-releasing hormone (34 units), 38% excited and 12% inhibited; angiotensin II (ANG II) (34 units), 26% excited, and 6% inhibited; somatostatin (14 units), 36% excited and 43% inhibited; serotonin (15 units), 67% excited and none inhibited; and dopamine (13 units), 46% excited and none inhibited. Of the units tested, 86% lay less than 100 microns from the ventricular surface. Units responsive to ANG II lay deeper than units responding to serotonin (P less than 0.005), osmotic changes (P less than 0.001), or carbamylcholine (P less than 0.02).

Action Potentials↗
PubMed1983

Extracellular recording in rat area postrema in vitro and the effects of cholinergic drugs, serotonin and angiotensin II.

Spontaneous extracellular action potentials were recorded from rat area postrema explants in vitro for up to 6 h at 35 degrees C. Their geometric mean frequency was 4.4 +/- 1.7-11 Hz (n = 120) and they were most often recorded caudal to the obex. The frequency of spontaneously discharging units could be increased three-fold by raising the KCl concentration from 5 to 15 X 10(-3) M but a claimed non-specific excitant of neurones, L-glutamic acid at 10(-7)-10(-3) M was without effect. Carbamylcholine at 10(-9)-10(-7) M increased the frequency of spontaneous units (12/13 trials) as did 10(-7) M neostigmine sulphate (14/14 trials). The effects of carbamylcholine and neostigmine were additive and were blocked by atropine sulphate at 10(-6) M (18/18 trials). Atropine also stopped the discharge of spontaneous units while D-tubocurarine did not affect unit discharge frequency. It is suggested that units responding to cholinergic drugs have an afferent input from the dorsal vagus. A number of putative transmitters, serotonin (10(-9)-10(-7) M), angiotensin II (0.5 X 10(-10)-0.5 X 10(-9) M) and dopamine (10(-9)-10(-5) M) which on indirect grounds are thought to affect area postrema neurones, were without effect on unit discharge frequency.

Afferent Pathways↗
PubMed1983

Localization and characteristics of responses in cat medial preoptic region to stimulation of fornix.

Field potentials and units were recorded within the boundaries of the cat medial preoptic area (MPO) following stimulation of the fornix. The position of the recording electrode was marked by pressure injection of alcian blue dye. Stimulation of the medial and lateral aspects of the ipsilateral fornix produced a field consisting of four negative waves and a positive wave. The first and second negative waves had a short latency and duration and appeared to be produced by fornix axons in the MPO. The third negative wave had a longer duration and appeared to be generated by the monosynaptic activation of units in the MPO. The fourth negative wave had a long latency and very long duration and appeared to be generated by polysynaptic activation of neurons in the MPO. The positive wave was associated with inhibition of MPO neurons as a result of fornix excitation of inhibitory interneurons. Responses from nerve fibers in the MPO had latencies corresponding to peaks of the first and second peaks of the evoked potential. Monosynaptically evoked responses to ipsilateral fornix stimulation were recorded all over the dorsal two-thirds of the MPO. Units driven from the medial fornix lay in the periventricular nucleus. Units driven from the lateral fornix lay in the medial preoptic nucleus. Units driven from both medial and lateral fornix lay between units driven by the medial fornix medially and the lateral fornix laterally. Units driven polysynaptically from the ipsilateral fornix lay in the medial preoptic nucleus. About one-quarter of such units were also excited by stimulation of the contralateral fornix. Spontaneously discharging units were recorded all over the MPO. The geometric mean frequency was 2.1 +/- 1.7-2.8 Hz; n = 35. Fornix stimulation inhibited spontaneous units in the medial preoptic nucleus for 50-200 ms. Usually inhibition was evoked by lateral fornix stimulation or by medial or lateral fornix stimulation. Spontaneously discharging units in the periventricular nuclei were not inhibited by fornix stimulation. The position of fornix-excited units suggests they might be temperature sensitive and in female animals, play a role in controlling ovulation.

Animals↗
PubMed1982

Histamine: correlative studies in nucleus accumbens.

The role of histamine as a neurotransmitter has been the subject of considerable controversy. Recent evidence suggests it to be involved in such complex activities as arousal and affect. The purpose of the present study is to examine the possible source, function, and pharmacology of histamine in the nucleus accumbens, an area of the brain also implicated in complex activities such as affect. The anatomical studies suggest that the most probable source of the histamine in nucleus accumbens is the complex region lateral to the mammillary nuclei. These areas are the intercalated nucleus and the tuberomammillary nucleus (nuclei gemini hypothalami). To a lesser degree, the supramammillary complex may also contribute histamine-containing axons to the accumbens area. Adenylate cyclase in the rabbit nucleus accumbens displayed activation in response to histamine agonists (histamine, 2-Me-histamine, and 4-Me-histamine). The action of the H1 antagonist promethazine was greater than the H2 antagonist metiamide in reducing enzyme activation by histamine and 2-Me-histamine. In contrast, metiamide was more potent than promethazine toward antagonism of the action of 4-Me-histamine. However, no additive effects were noted when agonists were added in combination. Based upon these data, it is suggested that activation of adenylate cyclase in the rabbit nucleus accumbens is mediated in part by mixed H1 and H2 receptors or cellular disruption reflects the loss of receptor specificity. Physiological studies demonstrated that the H2 agonist 4-Me-histamine had an inhibitory effect on the activity of neurons driven by stimulation of the fimbria. The magnitude of the effect was frequency dependent. The H1 agonist 2-Me-histamine had no significant effect. Iontophoretic application of 4-Me-histamine had minimal effect upon low frequency volleys (0.5 Hz) but had a pronounced effect upon higher frequency volleys (6.0 Hz). These effects were antagonized by metiamide. Iontophoretic application of metiamide alone produced an effect only upon the P component of the field response, which is also bicuculline sensitive. Bicuculline coadministration was also effective in antagonizing the 4-Me-histamine effect. The physiological data suggest that histamine works through H2 receptors in nucleus accumbens, perhaps by potentiating the effects of gamma-aminobutyric acid (GABA). Thus, histamine in nucleus accumbens appears to function as a modulatory substance whose effect is dependent upon the activity of other transmitter and afferent systems.

Adenylyl Cyclases↗
PubMed1982

Evidence for the role of non-quantal acetylcholine in the maintenance of the membrane potential of rat skeletal muscle.

1. Resting membrane potentials of rat diaphragm muscles cultured in Trowell T8 medium were measured in vitro. After 3 hr in culture the resting membrane potential of muscle fibres within 2.5 mm of nerve section (;near') was -68.3 +/- 0.4 mV (nineteen preparations). This was significantly lower (P < 0.001) than the resting potential (-74.0 +/- 0.4 mV) measured in muscle fibres 8-10 mm from the site of nerve section (;far') in the same preparations. A difference between the ;near' and the ;far' fibres was maintained in muscles cultured for 6 and 12 hr. Miniature end-plate potentials were present in both ;near' and ;far' fibres cultured for 3 and 6 hr and ceased after 12-15 hr.2. The presence of carbamylcholine (10(-7) or 10(-8) M) maintained the resting membrane potential of ;near' fibres close to that of ;far' fibres at 3, 6 and 12 hr. For example, at 3 hr in the presence of 10(-8) M-carbamylcholine the mean resting potential was 75.6 +/- 0.5 mV in ;near' fibres and 76.1 +/- 0.4 mV in ;far' fibres (four preparations). A similar effect was produced in preparations exposed to anticholinesterases: diisopropylphosphorofluoridate (DFP) (10(-7) M), neostigmine (10(-7) M) or physostigmine (10(-5) M).3. Agents that blocked acetylcholine receptors had the reverse effect. In the presence of alpha-bungarotoxin (1 mug/ml.) or d-tubocurarine (10(-5) M) the resting membrane potential of ;far' fibres was reduced to the level of ;near' fibres over the 24 hr period of observation. For example, at 3 hr in the presence of alpha-bungarotoxin the mean resting potential was 67.2 +/- 0.5 mV in ;near' fibres and 68.5 +/- 0.6 mV in ;far' fibres (six preparations). The effect of d-tubocurarine was reversible.4. When muscles were cultured in Ca(2+)-free medium containing 1 mM-EGTA and 10 mM-Mg(2+), there was no difference in membrane potential between ;near' and ;far' fibres and physostigmine (10(-5) M) was ineffective in raising the membrane potential of ;near' fibres.5. It is suggested that non-quantal acetylcholine released from nerve terminals maintains the membrane potential of muscle fibres through a Ca(2+)-dependent mechanism.

Acetylcholine↗
PubMed1981

Localization of immunoreactive angiotensin II in the hippocampus and striatum of rat brain.

Angiotensin II (ANG II) was estimated by radioimmunoassay in extracts of rat brain. In extracts of whole brain the mean content was 108 +/- 16 fmol/g and estimates of ANG II in kidney and plasma were similar to previous reports. A regional distribution of ANG II was determined. Hippocampus had the highest concentration and cortex the lowest. The concentrations relative to cortex were: hippocampus, 8; striatum, 5; cerebellum, 4; hypothalamus:thalamus:septum:midbrain (HTSM), 3; and medulla, 3.

Angiotensin II↗