Faculty Bibliography

Single pulse stimuli were delivered to the Schaffer collaterals in the in vitro hippocampal slice preparation. Local application of bicuculline to the CA3 region resulted in a series of population cell bursts in CA3, resembling the neuronal patterns which occur in the normal, freely moving rat during hippocampal sharp waves. These bicuculline-induced cell bursts in CA3 resulted in long-term potentiation (LTP) of the CA1 response. These findings suggest that the naturally occurring hippocampal sharp waves may reflect events analogous to artificially induced LTP

Hippocampal tissue derived from 12-, 20-, 25- and 34-mm rat fetuses was placed in a cavity formed by unilateral aspiration of the fimbria-fornix and the overlying neocortical tissue in adult rats. From 4 to 6 months after transplantation the rats were equipped with chronic recording and stimulating electrodes. Single cell activity of the transplant was monitored during running in a wheel, drinking, and sleeping. Both complex-spike cells (n = 151) and single-spike cells (n = 80) were recorded from the graft. A portion of the neurons changed their firing rates and discharge patterns as a function of ongoing behavior. About half of the single-spike cells increased their firing frequency during running. Fifteen per cent of the single-spike cells fired rhythmically at about 8 Hz during running, and the paradoxical phase of sleep and the discharge pattern correlated with rhythmic slow activity (theta) recorded concurrently from the contralateral (intact) hippocampus. These patterns were most frequently obtained from grafts of 20- and 25-mm (16 to 18 embryonic days) fetuses. Graft neurons could be activated by stimulating the ipsilateral hippocampus or the ipsilateral perforant path, with latencies of 8-30 ms. The most common electrical pattern in grafts of all groups was the synchronous bursts of several neighboring cells and concurrent electroencephalogram sharp-waves. Sharp-waves occurred during all behaviors. Large amplitude, high-frequency electroencephalogram spindles (14-18 Hz and 30-50 Hz) and associated neuronal bursts were recorded in grafts of 12-, 20-, and 25-mm fetuses. Based on these findings we suggest that both subcortical afferents and host hippocampal afferents send axons to hippocampal grafts and form viable synaptic connections with a portion of the neurons in the graft. The frequently encountered population bursts are explained by assuming that excitatory collaterals in the graft are more potent in the graft than in the normal hippocampus, and/or GABAergic inhibition is less efficient in the graft

Solid pieces of the fetal septal region (SG) or hippocampus (HPC) were implanted in a cavity formed by aspiration of the fimbria fornix (FF) and the overlying cingulate cortex on one side in adult rats. In other lesioned animals cell suspensions obtained from the fetal septal area (SS) or the locus coeruleus region of the brainstem (LC) were injected stereotaxically into the deafferented host hippocampus. Six to 9 months after transplantation the animals had chronic recording electrodes implanted into both hippocampi. EEG and unit activity were monitored during running in a wheel, drinking and immobility. Unilateral fimbria-fornix lesions abolished rhythmic slow activity (RSA or theta, theta) in the ipsilateral hippocampus and no recovery was seen up to 9 months later in either the control FF-lesioned animals or in the rats with LC suspension grafts. Recovery of RSA, however, was observed in all animals with solid septal grafts and in some rats with solid HPC grafts. Similar to normal rats, RSA was present only during running and absent during drinking and sitting still. Coherence measurements of RSA between the transplanted and intact hemispheres resulted in high values (0.70-0.95). Concurrent with RSA, interneurons and granule cells in the host hippocampus fired rhythmically at RSA frequency (6-9 Hz). The depth profile and the antero-posterior distribution of the power of RSA correlated with the amount and distribution of the graft-induced acetylcholinesterase-positive reinnervation of the host hippocampus. In contrast to the animals with solid septal grafts, placed within the FF lesion cavity, the rats with intrahippocampal septal suspension grafts displayed only short duration bursts of RSA, and mainly during immobility. Based on these findings it is suggested that at least a proportion of the RSA 'pacemaker' cells of the host septum survives the transection of the fimbria-fornix fibers and that a graft of fetal septal or hippocampal tissue implanted into the lesion cavity may be capable of relaying this pacemaker activity to the host hippocampus. This effect may be due to the ability of the grafted tissue to promote the regeneration of new, direct or indirect, septo-hippocampal connections across the lesion cavity

Adult rats with unilateral aspirative lesions of the fimbria-fornix and the overlying cingulate cortex received implants of 17-day-old fetal hippocampal tissue in the lesion cavity, placed to form a tissue bridge across the cavity. From 6 to 8 months later they were equipped with chronic recording and stimulating electrodes in the transplant and the host brain. The dominant electrical pattern of the graft consisted of irregularly occurring sharp waves (SPW) or EEG spikes of 30-150 ms duration and concurrent synchronous neuronal bursts of large cell populations. SPWs occurred during all behaviors but their frequency was significantly lower during running than during drinking. Population bursts of neurons in the graft could be evoked by stimulating either the ipsilateral host hippocampus or the perforant path. Both complex spike cells and single spike cells could be recorded from the graft. The discharge frequency of single spike cells was considerably higher during running than during drinking or immobility. Some of the single spike cells in the graft fired rhythmically at 6-9 Hz during running and walking, and phase-locked with the rhythmic slow EEG activity (theta, theta-EEG) recorded from the intact host hippocampus. Occasionally field theta-EEG was also present in the graft. These findings suggest that at least a portion of the graft neurons had come under the control of the host brain, and by way of the newly established host-graft connections the activity of some graft neurons was regulated in a near-normal manner

3H-glycine was applied to the cat cerebellar cortex under resting conditions and during inferior olive stimulation which activated the climbing fiber system on a restricted area. Electric recording was made. The autoradiograms showed, that under resting condition labelled glycine was incorporated mainly in granule, Golgi and basket cells and only a few Purkinje and stellate cells were active. Also cerebellar glomeruli remained without labelling. On climbing fiber stimulation Purkinje cells became activated singly and grouped, also Golgi and stellate cells increased in number. Granule cells were totally inhibited. 3H-glycine, when applied to the rat hippocampus, the dentate gyrus, CA1 and CA4 fields showed labelling at low frequency stimulation. When 400 Hz high frequency stimulation periods were interposed, long-term potentiation ensued. The overall labelling of each hippocampal region was intensified significantly, indicating that glycine incorporation may be a sign not only of excitation but also of long-term potentiation. 3H-glycine was applied to frog spinal cord during rest and dorsal root stimulation. Interneurons and motor neurons excited by the afferent fibers showed intensive glycine uptake. It is concluded that the glycine labelling method is suitable for detecting neural excitation in the structures dealt with in this paper

Hippocampal EEG was recorded in behaving rats in which the brain stem afferents to the septal region were previously damaged. In these animals rhythmic slow activity (RSA or theta) was continuously present, including drinking and immobility. The average frequency of RSA, however, was significantly higher during running (8-9 Hz) than during drinking or awake motionless state (6-8 Hz). In normal rats irregular sharp waves, rather than RSA were present during drinking and immobility. The results suggest that brain stem afferents are necessary to suppress the rhythmic firing of septal 'pacemaker' cells

This study investigated the spatial distribution and cellular-synaptic generation of hippocampal sharp waves (SPW) in the dorsal hippocampus of the awake rat. Depth analyses of SPWs were performed by stepping the recording electrode in 82.5 microns increments. SPWs were present during slow wave sleep, awake immobility, drinking, grooming and eating (0.01-2/s). The largest negative SPWs were recorded from the middle part of the stratum radiatum of CA1, the stratum lucidum of CA3, the inner molecular layer of the dentate gyrus and from layer I of the subiculum, in that order. The polarity of the SPWs was positive in layers II-IV of the subiculum, in stratum oriens and stratum pyramidale of CA1 and CA3, and in the hilus of the dentate gyrus. The electrical gradients across the null zones of the field SPWs were as large as 8-14 mV/mm. SPWs were associated with population bursts of pyramidal cells and increased discharges of interneurons and granule cells. During the SPW the excitability of granule cells and pyramidal cells to afferent volleys increased considerably. Picrotoxin and atropine and aspiration lesion of the fimbria-fornix increased either the amplitude or the frequency of SPWs. Diazepam and Nembutal could completely abolish SPWs. It is suggested that: hippocampal SPWs are triggered by a population burst of CA3 pyramidal cells as a result of temporary disinhibition from afferent control; and field SPWs represent summed extracellular PSPs of CA1 and subicular pyramidal cells, and dentate granular cells induced by the Schaffer collaterals and the associational fibers of hilar cells, respectively. The relevance of the physiological SPWs to epileptic interictal spikes and long-term potentiation is discussed

Averaged evoked potentials and unitary discharges in response to tooth pulp and acoustic click stimuli were recorded from the hippocampus of freely moving rats. The spatial distribution of evoked field responses to tooth pulp stimulation and acoustic clicks were identical. Averaged evoked potentials consisted of a large negative deflection (N1) preceded by a small positive potential (P1). The shortest latency N1 in response to tooth pulp stimulation was recorded from the middle third of the dentate molecular layer and the outer portion of apical dendrites of CA3 (27 ms). The peak latency of N1 was significantly longer (34 ms) in the stratum radiatum of CA1. Laminar profiles of N1 in the dentate gyrus and CA3 were similar to that evoked by electrical stimulation of the medial entorhinal afferents; in CA1 the depth profiles of the potentials were similar to the response profile evoked by the Schaffer collaterals. Largest amplitude P1 was obtained from above the pyramidal layer of CA1 and the hilus. Both sensory modalities were able to modify the discharge rate of neurons in all hippocampal regions. The amplitude of evoked field potentials and cellular responses were dependent upon both the ongoing behavior of the animal and the nature of its response to the stimulus. The largest amplitude evoked potentials were recorded during immobility and slow wave sleep. On the other hand, virtually no potentials were obtained during exploratory behaviors associated with theta EEG activity. The findings indicate that information about sensory stimuli can reach the hippocampus by two distinctive pathways: a short latency inhibitory input via the fimbria-fornix and a longer latency path via the entorhinal cortex. It is suggested that neuronal mechanisms involved in theta EEG block the sequential activation of the unidirectional entorhinal-hippocampal circuitry

Rats with dorsal hippocampal (HIPP) and cortical (CX) lesions and control animals were tested for acquisition of a differential reinforcement of low rate of responding (DRL-20 s) task in a 6-compartment apparatus that permitted running, drinking and other activities. HIPP and CX animals and one group of control rats (NOR) were trained in an 'open' condition which allowed a variety of activities, while another control group (CON) were trained while confined to the food and lever area of the apparatus. In the second stage of the experiment conditions were reversed. DRL performance was significantly better in the 'open' condition for all groups: more pellets were gained with fewer lever presses. Groups HIPP performed worse than groups NOR and CX in both conditions. When NOR and CX rats were confined to the food area they developed a jumping behaviour, (attempts to leave the food area) which increased throughout the testing period, coupled with a progressive deterioration of performance. Rats initially trained in the 'confined' condition did not develop jumping. HIPP animals were significantly more active; they produced more lever presses, entered the different compartments more frequently and showed higher activity in the running wheel. The schedule-induced interim behaviour in the open condition was wheel-running in all groups. In the HIPP group the number of jumps was significantly less than in the NOR and CX groups i.e. they were less affected by confinement. These findings suggest that previous experience in the 'open' condition has a strong anterograde, seemingly irreversible, consequence on subsequent behaviour in the 'confinement' condition for normal and cortical control rats and this anterograde effect is less pronounced in animals with hippocampal damage