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Biomedical subjects

G R Poe

Publications and source records attributed to G R Poe.

14 recordsLinked to original sources

Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep.

The idea that sleep could serve a cognitive function has remained popular since Freud stated that dreams were "not nonsense" but a time to sort out experiences [S. Freud, Letter to Wilhelm Fliess, May 1897, in The Origins of Psychoanalysis - Personal Letters of Sigmund Freud, M. Bonaparte, A. Freud, E. Kris (Eds.), Translated by E. Mosbacher, J. Strachey, Basic Books and Imago Publishing, 1954]. Rapid eye movement (REM) sleep, which is associated with dream reports, is now known to be is important for acquisition of some tasks [A. Karni, D. Tanne, B.S. Rubenstein, J.J.M. Askenasy, D. Sagi, Dependence on REM sleep of overnight improvement of a perceptual skill, Science 265 (1994) 679-682; C. Smith, Sleep states and learning: a review of the animal literature, Biobehav. Rev. 9 (1985) 157-168]; although why this is so remains obscure. It has been proposed that memories may be consolidated during REM sleep or that forgetting of unnecessary material occurs in this state [F. Crick, G. Mitchison, The function of dream sleep, Nature 304 (1983) 111-114; D. Marr, Simple memory: a theory for archicortex, Philos. Trans. R. Soc. B. 262 (1971) 23-81]. We studied the firing of multiple single neurons in the hippocampus, a structure that is important for episodic memory, during familiar and novel experiences and in subsequent REM sleep. Cells active in familiar places during waking exhibited a reversal of firing phase relative to local theta oscillations in REM sleep. Because firing-phase can influence whether synapses are strengthened or weakened [C. Holscher, R. Anwyl, M.J. Rowan, Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo, J. Neurosci. 15 (1977) 6470-6477; P.T. Huerta, J.E. Lisman, Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro, Neuron 15 (1995) 1053-1063; C. Pavlides, Y.J. Greenstein, M. Grudman, J. Winson, Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm, Brain Res. 439 (1988) 383-387] this experience-dependent phase shift, which developed progressively over multiple sessions in the environment, is consistent with the hypothesis that circuits may be restructured during REM sleep by selectively strengthening recently acquired memories and weakening older ones.

Animals↗

Partial hippocampal inactivation: effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems.

Age Factors↗

Relationships between hippocampal activity and breathing patterns.

Single cell discharge, EEG activity, and optical changes accompanying alterations in breathing patterns, as well as the knowledge that respiratory musculature is heavily involved in movement and other behavioral acts, implicate hippocampal regions in some aspects of breathing control. The control is unlikely to reside in oscillatory breathing movements, because such patterns emerge in preparations retaining only the medulla (and perhaps only the spinal cord). However, momentary changes in breathing patterns induced by affect, startle, whole-body movement changes, or compensatory ventilatory changes mediated by rostral brain regions likely depend on hippocampal action in aspects of control. Hippocampal activity was enhanced prior to sighs, and this enhancement was accompanied by increased slow theta activity. Theta frequency increased during apnea, prior to return of breathing. Consideration of hippocampal contributions to breathing control should be viewed in the context that significant interactions exist between blood pressure changes and ventilation, and that modest breathing challenges, such as exposure to hypercapnia or to increased resistive loads, bring into action a vast array of brain regions involving nearly every level of the neuraxis.

Animals↗

A miniature CCD video camera for high-sensitivity light measurements in freely behaving animals.

We developed a miniaturized, high-sensitivity camera that can be placed in areas of difficult access in freely behaving animals for neural tissue imaging. The device consists of a charged coupled device (CCD) chip, a coherent image conduit and miniature light emitting diodes (LEDs). An amplifier circuit is constructed on the camera chip and nine wires are attached for external connections. Placement of LEDs around the image conduit perimeter provides dark-field illumination, which increases detection of cellular-related light scattering changes and doubles the depth-of-view over conventional reflectance imaging procedures. The device has been successfully used to record from several deep brain structures, including the ventral medullary surface of sleeping and waking cats. The procedure allows assessment of light scattering changes that result from neural activity or detection of vital dyes to metabolic or voltage-induced activation.

Analysis of Variance↗

Activity changes of the cat paraventricular hypothalamus during phasic respiratory events.

We monitored the spatiotemporal organization of cellular activity in the medial paraventricular hypothalamus during spontaneously-occurring periods of increased inspiratory effort followed by prolonged respiratory pauses (sigh/apnea) in the freely-behaving cat. Paraventricular hypothalamic activity was assayed by video images of light captured with a stereotaxically-placed fibre optic probe. Respiratory activity was measured through electromyographic wire electrodes placed in the diaphragm. Sigh/apnea events appeared in all behavioural states, and especially during quiet sleep. Overall paraventricular hypothalamic activity declined transiently, with the onset of decline coinciding with the beginning of the sigh inspiratory effort, reached a nadir at apnea onset 4.4+0.5 s from the beginning of the sigh, increased during the course of the apnea, and subsequently rebounded above baseline to peak at 10.9+2.5 s after sigh onset. Scattered, small areas of the imaged region were activated or depressed independently of the overall image values. The data suggest that paraventricular hypothalamic activity changes dynamically during phasic respiratory events, and may contribute to the progression of the sigh/apnea. We speculate that the medial paraventricular hypothalamus influences breathing patterns through projections to parabrachial respiratory phase-shift regions, and that longer-latency influences may also be exerted indirectly through blood pressure effects from paraventricular hypothalamic projections to medullary cardiovascular nuclei. Additionally, the paraventricular hypothalamus may convey respiratory influences from other rostral structures, such as the hippocampus.

Animals↗

Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation.

We assessed relationships of evoked electrical and light scattering changes from cat dorsal hippocampus following Schaeffer collateral stimulation. Under anesthesia, eight stimulating electrodes were placed in the left hippocampal CA field and an optic probe, coupled to a photodiode or a charge-coupled device camera to detect scattered light changes, was lowered to the contralateral dorsal hippocampal surface. Light at 660 +/- 10 (SE) nm illuminated the tissue through optic fibers surrounding the optic probe. An attached bipolar electrode recorded evoked right hippocampal commissural potentials. Electrode recordings and photodiode output were simultaneously acquired at 2.4 kHz during single biphasic pulse stimuli 0.5 ms in duration with 0.1-Hz intervals. Camera images were digitized at 100 Hz. An average of 150 responses was calculated for each of six stimulating current levels. Stimuli elicited a complex population synaptic potential that lasted 100-200 ms depending on stimulus intensity and electrode position. Light scattering changes peaked 20 ms after stimuli and occurred simultaneously with population spikes. A long-lasting light scattering component peaked 100-500 ms after the stimulus, concurrently with larger population postsynaptic potentials. Optical signals occurred over a time course similar to that for electrical signals and increased with larger stimulation amplitude to a maximum, then decreased with further increases in stimulation current. Camera images revealed a topographic response pattern that paralleled the photodiode measurements and depended on stimulation electrode position. Light scattering changes accompanied fast electrical responses, occurred too rapidly for perfusion, and showed a stimulus intensity relationship not consistent with glial changes.

Animals↗

State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging.

Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz during spontaneously varying sleep/waking states. Sequential state transitions from active waking to quiet waking, quiet sleep and active sleep were accompanied by progressively increased levels of PVH activity. Overall activity was highest during active sleep, and decreased markedly upon awakening. Moment-to-moment activity oscillated in the 0-0.1 Hz range, especially during active sleep and active waking; this oscillation diminished during quiet sleep. Distinct sub-regions of enhanced or diminished activity emerged within the imaged area in a state-dependent manner. We conclude that PVH activity changes with behavioral state in a regionally specific manner, and that overall activity increases during quiet sleep, and is even more enhanced in active sleep. PVH activation could be expected to stimulate pituitary release of adrenocorticotropic hormone (ACTH) and affect input to autonomic regulatory sites. Since ACTH and corticotropin releasing factor elicit arousal, and since the PVH projects to other brain areas which modulate state, we speculate that the PVH plays a role in shaping characteristics of sleep/waking states.

Animals↗

Concurrent reflectance imaging and microdialysis in the freely behaving cat.

We present a method to perform simultaneous microdialysis with light reflectance imaging of neural activity in a discrete brain region of the freely behaving animal. We applied this method to the dorsal hippocampus of freely behaving cats to (1) measure extracellular glutamate and reflectance variations across a sleep-waking cycle, (2) assess spatially coherent neural activity changes accompanying local perfusion of cocaine and (3) measure local changes in cell volume induced by infusion of hyper- and hypo-osmotic solutions. Higher extracellular glutamate concentrations corresponded to higher imaged neural activity. Sequential images showed that cocaine perfusion elicited a propagating reflectance change as cocaine reached the tissue. Microperfusion of hypo-osmotic solution ( - 100 mOsm), which increases cell volume, decreased reflectance. Microperfusion of hyperosmotic sucrose solutions, which reduce cell volume, increased reflectance in a dose-dependent manner. The data indicate that reflectance imaging can measure changes in cell volume, and could, thus, measure neural activity through activity/cell volume corollaries. Combining microdialysis and optical imaging enables investigation of the neurochemical bases of spontaneous neural activity patterns within discrete brain nuclei.

Animals↗

Hippocampal activity during transient respiratory events in the freely behaving cat.

We measured dorsal hippocampal activity accompanying sighs and apnea using reflectance imaging and electrophysiologic measures in freely behaving cats. Reflected 660-nm light from a 1-mm2 area of CA1 was captured during sighs and apnea at 25 Hz through a coherent image conduit coupled to a charge coupled device camera. Sighs and apnea frequently coincided with state transitions. Thus, state transitions without apnea or sighs were separately assessed to control for state-related activity changes. All dorsal hippocampal sites showed discrete regions of activation and inactivation during transient respiratory events. Imaged hippocampal activity increased 1-3 s before the enhanced inspiratory effort associated with sighs, and before resumption of breathing after apnea. State transitions lacking sighs and apnea did not elicit analogous optical activity patterns. The suprasylvian cortex, a control for site, showed no significant overall reflectance changes during phasic respiratory events, and no discrete regions of activation or inactivation. Spectral estimates of hippocampal electroencephalographic activity from 0-12 Hz showed significantly increased power at 3-4 Hz rhythmical slow activity before sighs and apnea, and increased 5-6 Hz rhythmical slow activity power during apnea, before resumption of breathing. Imaged activity and broadband hippocampal electroencephalogram power decreased during sighs. We propose that increased hippocampal activity before sigh onset and apnea termination indicates a role for the hippocampus in initiating inspiratory effort during transient respiratory events.

Animals↗

Imaging the dorsal hippocampus: light reflectance relationships to electroencephalographic patterns during sleep.

We assessed the correspondence of 660 nm light reflectance changes from the dorsal hippocampus with slow wave electroencephalographic (EEG) activity during quiet sleep (QS) and rapid eye movement (REM) sleep in four cats. An optic probe, attached to a charge-coupled-device (CCD) video camera, was placed on the dorsal hippocampal surface to collect reflectance images simultaneously with EEG, which was measured by macroelectrodes placed around the probe circumference. Spectral estimates of EEG and light reflectance amplitude indicated that reflectance changes occurred in a similar frequency range as EEG changes. Dividing the image into 10 subregions revealed that reflectance changes at the rhythmical slow wave activity band (RSA, 4-6 Hz) persisted in localized regions during QS and REM sleep, but regional changes showed considerable wave-by-wave independence between areas and from slow wave electrical activity. Peak frequencies for reflectance changes corresponded to fast RSA frequencies observed in the EEG. Optical changes most likely derive from fast-acting physical phenomena, rather than from alterations in blood perfusion, and provide increased spatial resolution over that offered by electrical measurements.

Animals↗

Hippocampal reflected optical patterns during sleep and waking states in the freely behaving cat.

We examined reflected light as a measure of neural activity from a 2 mm2 area of dorsal hippocampus and surrounding neocortex in nine freely behaving cats during sleep and waking states. Light reflectance at 660 or 700 nm was measured by a coherent fiber optic probe attached to a charge-coupled device video camera that allowed acquisition of images from subcortical structures. In the dorsal hippocampus, rapid eye movement sleep (REMS) and active waking (AW) resulted in a significant decline (-0.9% +/- 0.3 and -2.0% +/- 0.5, respectively) in overall reflected light from the dorsal hippocampus relative to quiet sleep (QS), while quiet waking (QW) resulted in an overall increase (+2.0% +/- 0.4). In the neocortical probe placement group, reflectance also decreased during AW (-1.6% +/- 0.5) and increased during QW (+1.7 +/- 0.6) as compared to QS. In contrast to the hippocampus, however, overall reflectance increased, rather than decreased, in the neocortex during REMS (+2.7% +/- 1.3). We interpret a decline in reflectance as representing increased activation of underlying neural tissue. Thus, the cat dorsal hippocampus increased overall activity during REMS as compared to QS, while neocortical structures decreased overall activity during the same state. These results concur with expected activity changes based on electrophysiologic and autoradiographic studies. The imaging procedure provided a continuous assessment of spatially organized neural activity changes in the freely behaving animal.

Animals↗

Imaging of hippocampal and neocortical neural activity following intravenous cocaine administration in freely behaving cats.

We examined spatial-temporal patterns of neural activity, as inferred from 700 nm light reflectance, from the dorsal hippocampus and surrounding neocortex in seven freely behaving cats following 1.5, 2.5, 3.5 and 5.0 mg/kg intravenous cocaine administration. Images were acquired using a new technique which gathered reflected light from cortical and subcortical structures. Cardiac and respiratory patterning, collected simultaneously with optical images, revealed increased rates and diminished variation after intravenous cocaine administration. Cocaine increased reflectance correlates of hippocampal neural activity in a dose-dependent fashion over a 120 min period, with a lengthening time-to-peak effect (22-76 min). The largest dose resulted in an initial decrease, followed by the greatest enhancement in neuronal activity. Correlates of neural activation in the neocortex displayed an inverse dose-response curve to that found in the hippocampus; the time-to-peak effect was shorter (6-43 min) and the maximal change was reduced. Regional patches and bands of activation occurred during the period of the cocaine response, and were more pronounced in the hippocampus than the neocortex. Procaine, administered in a similar dose, slightly increased neural activity for 10 min in both the hippocampus and neocortex, and elicited a small increase in respiration. Cocaine induces a pronounced enhancement of neural activation in the neocortex and dorsal hippocampus; the time course of activation in the hippocampus parallels an increased respiratory pattern and outlasts the neocortical response. We speculate that hippocampal activation may be related to the profound respiratory acceleration found in response to cocaine.

Animals↗