Septal Modulation of the Hippocampus

The medial septum (MS) is the main source of acetylcholine to the hippocampus, a structure involved in memory and Alzheimer’s disease (AD). Learning and memory involve long-term changes in synaptic strengths, and are suggested to be facilitated by a brain wave, theta rhythm in the hippocampus. Since medial septal neurons influence hippocampal neural activity, lesion of two neuronal populations in the MS, cholinergic and GABAergic, was performed by intraseptal infusion of 192 IgG-saporin and orexin-saporin, respectively. I hypothesized that 1) activation of cholinergic cells by vestibular stimulation induces an atropine-sensitive theta rhythm, modulates synaptic transmission and enhances long-term potentiation (LTP), a model of synaptic plasticity, in the hippocampus and 2) GABAergic neurons regulate granule cell activity by inhibiting interneurons in the dentate gyrus (DG). Vestibular stimulation by passive whole-body rotation induced an atropine-sensitive theta rhythm that was not present in awake immobility. Following systemic cholinergic blockade, septal 192 IgG-saporin or bilateral vestibular lesion, rotation-induced theta and rotation-induced modulation of evoked potential were attenuated. LTP was enhanced when tetanus was delivered during rotation as compared to during immobility. Systemic cholinergic blockade or 192 IgG-saporin lesion abolished LTP enhancement by rotation. I provided the first report investigating the role of septal GABAergic neurons on dentate neuronal unit activity in vivo. In urethane-anesthetized sham-lesion rats, pontis nucleus oralis (PNO) stimulation induced a theta rhythm, increased spontaneous granule cell activity, facilitated DG population spike and increased paired-pulse depression (PPD) of population spikes. In freely moving rats, PPD was larger during walking as compared to during immobility. Orexin-saporin lesion attenuated theta, and blocked PNO-induced population spike facilitation and PPD in anesthetized rats. Spontaneous granule cell activity decreased while spontaneous interneuronal activity increased in orexin-saporin lesion rats as compared to sham-lesion rats. It is inferred that tonic interneuronal inhibition is increased and granule cells are less likely to be activated in orexin-saporin lesion rats, as compared to sham-lesion rats. Therefore, vestibular stimulation provides a physiological method to activate septal cholinergic neurons, consistent with improvement of cognition in humans. Vestibular stimulation may ameliorate cholinergic dysfunction deficits and targeting septal GABAergic neurons may improve behavioral functions in AD

Medial septal cholinergic neurons modulate isoflurane anesthesia.

BACKGROUND: Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known. METHODS: Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by counting choline acetyltransferase-immunoreactive cells and parvalbumin-immunoreactive cells. RESULTS: Rats with 192 immunoglobulin G-saporin lesion, as compared with control rats with sham lesion, showed a 85% decrease in choline acetyltransferase-immunoreactive, but not parvalbumin-immunoreactive, neurons in the medial septal area. Lesioned as compared with control rats showed increased isoflurane sensitivity, characterized by a leftward shift of the graph plotting cumulative LORR percent with isoflurane dose. However, lesioned and control rats were not different in their LORR sensitivity to ketamine. When administered with 1.375% isoflurane, LORR induction time was shorter, whereas emergence time was longer, in lesioned as compared with control rats. Hippocampal 62-100 Hz gamma power in the electroencephalogram decreased with isoflurane dose, with a decrease that was greater in lesioned (n = 5) than control rats (n = 5). CONCLUSIONS: These findings suggest a role of the septal cholinergic neurons in modulating the sensitivity to isoflurane anesthesia, which affects both induction and emergence. The sensitivity of hippocampal gamma power to isoflurane appears to indicate anesthesia (LORR) sensitivity

Hippocampal nociceptive activation in the rat

Master'sMASTER OF SCIENC

Vestibular stimulation enhances hippocampal long-term potentiation via activation of cholinergic septohippocampal cells.

Vestibular stimulation induced acetylcholine release in the hippocampus, and acetylcholine is known to facilitate long-term potentiation (LTP) in the hippocampus. Thus, we hypothesize that vestibular stimulation enhances LTP in CA1 in freely behaving rats, and this enhancement depends on the activation of septohippocampal cholinergic neurons. Field excitatory postsynaptic potentials were recorded in CA1 area of behaving rats following stimulation of the basal dendritic afferents. LTP was induced by a single stimulation train (100 pulses at 200 Hz) during passive whole-body rotation or during awake-immobility. LTP induced during rotation was significantly larger than that induced during immobility. Pretreatment with cholinergic antagonist atropine sulfate (50mg/kg i.p.) abolished the facilitation of LTP during rotation as compared to immobility. Selective lesion of cholinergic cells in the medial septum (MS) with 192 IgG-saporin (0.49 μg in 1.4 μl) also abolished the difference in LTP induced during rotation and immobility, which was found in sham-lesion rats. 192 IgG-saporin lesioned rats, as compared to sham-lesion rats, revealed a depletion of MS cells immunopositive to choline acetyltransferase and paling of acetylcholinesterase staining in the hippocampus, without significant change in the number of parvalbumin-immunopositive cells. We conclude that enhancement of LTP during vestibular stimulation is mediated by the activation of cholinergic septohippocampal cells. This is the first direct evidence that vestibular stimulation facilitates hippocampal synaptic plasticity via a cholinergic input

Septohippocampal GABAergic neurons mediate the altered behaviors induced by n-methyl-D-aspartate receptor antagonists.

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than in sham-lesion rats. MK-801 (0.5 mg/kg i.p.) induced hyperlocomotion associated with an increase in frequency, but not power, of the hippocampal theta in both ore-SAP and sham-lesion rats. However, MK-801 induced an increase in 71-100 Hz gamma waves in sham-lesion but not ore-SAP lesion rats. In sham-lesion rats, MK-801 induced an increase in locomotion and an impairment of prepulse inhibition (PPI), and ketamine (3 mg/kg s.c.) induced a loss of gating of hippocampal auditory evoked potentials. MK-801-induced behavioral hyperlocomotion and PPI impairment, and ketamine-induced auditory gating deficit were reduced in ore-SAP rats as compared to sham-lesion rats. During baseline without drugs, locomotion and auditory gating were not different between ore-SAP and sham-lesion rats, and PPI was slightly but significantly increased in ore-SAP as compared with sham lesion rats. It is concluded that septohippocampal GABAergic neurons are important for the expression of hyperactive and psychotic symptoms an enhanced hippocampal gamma activity induced by ketamine and MK-801, and for generating an atropine-resistant theta. Selective suppression of septohippocampal GABAergic activity is suggested to be an effective treatment of some symptoms of schizophrenia

Bank settlement plan Singapore

A BSP is a payment and settlement system between travel agents and airlines. It is certainly an effective payment system, greatly minimising the contacts between travel agents and airlines. Industry support for this new system is reflected in the accreditation of 163 agents from the mere fwe agents when it was first introduced on 16 October 1991. 'This project discusses the operations of BSP Singapore, its benefits especially to agents and airlines and the possibility of applying its concepts to the shipping industry. In due course, we hope that this study will serve as an useful reference, providing interested parties with a basic waking knowledge of BSP Singapore.BUSINES

Bank settlement plan Singapore

A BSP is a payment and settlement system between travel agents and airlines. It is certainly an effective payment system, greatly minimising the contacts between travel agents and airlines. Industry support for this new system is reflected in the accreditation of 163 agents from the mere fwe agents when it was first introduced on 16 October 1991. 'This project discusses the operations of BSP Singapore, its benefits especially to agents and airlines and the possibility of applying its concepts to the shipping industry. In due course, we hope that this study will serve as an useful reference, providing interested parties with a basic waking knowledge of BSP Singapore.BUSINES

Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulation.

The vestibular system has been suggested to participate in spatial navigation, a function ascribed to the hippocampus. Vestibular stimulation during spatial navigation activates a hippocampal theta rhythm (4-10 Hz), which may enhance spatial processing and motor response. We hypothesize that a cholinergic, atropine-sensitive theta is generated during passive whole-body rotation in freely behaving rats. Hippocampal EEGs were recorded by implanted electrodes in CA1 while rats were rotated on a vertical axis, for a minute or longer, at different angular velocities. Rotation induced a continuous hippocampal theta rhythm while the rat was immobile, in both light and dark conditions. Theta peak frequency showed a significant increase during high (50-70 rpm) as compared with a lower (20-49 rpm) rotational velocity. Rotation-induced theta was abolished by muscarinic receptor antagonist atropine sulfate (50 mg/kg i.p.) but not by atropine methyl nitrate (50 mg/kg i.p.), which did not pass the blood-brain barrier. Theta was attenuated in rats in which cholinergic neurons in the medial septum (MS) were lesioned with 192 IgG-saporin (0.14 μg in 0.4 μl), as confirmed by depletion of MS cells immunoreactive to choline acetyltransferase and an absence of acetylcholinesterase staining in the hippocampus. Bilateral lesion of the vestibular receptors by sodium arsanilate (30 mg in 0.1 ml, intratympanically) also attenuated the rotation-induced theta rhythm. In intact rats, field excitatory postsynaptic potentials (fEPSPs) in CA1 evoked by commissural stimulation were smaller during walking or rotation as compared with during immobility. Modulation of fEPSP was absent following atropine sulfate in intact rats and in 192 IgG-saporin lesion rats. In summary, this is the first report of a continuous atropine-sensitive hippocampal theta in the rat induced by vestibular stimulation during rotation, and accompanied by cholinergic modulation of hippocampal synaptic transmission. Vestibular-activated septohippocampal cholinergic activity could be an important component in sensorimotor processing and spatial memory