Jonathan Winson

Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of θ-rhythm ☆

Abstract Long-term potentiation (LTP), a long lasting enhancement of synaptic efficacy is considered a model for learning and memory. In anesthetized rats, θ-rhythm was induced in the dentate gyrus by midbrain stimulation. Short trains of pulses were applied to the perforant pathway either at the peak of θ-rhythm or its trough. Trains applied at the peak of θ-rhythm induced LTP while trains applied at the trough produced a decrease of synaptic efficacy or had no effect. Thus, θ-rhythm may play a modulating role in the induction of LTP, suggesting a possible mnemonic function for the rhythm during the behaviors in which it occurs.

Patterns of hippocampal theta rhythm in the freely moving rat

Abstract Theta activity was investigated during the two behavioral states in which this activity occurs in the freely moving rat, namely, movement (such as exploration) and paradoxical sleep. The patterns of theta activity are basically the same in both conditions. Dorsoventral microelectrode penetration of the dorsal hippocampus shows a maximal amplitude of activity in the CA 1 pyramidal layer. With further penetration, the theta activity gradually reverses phase, the reversal being complete at the hippocampal fissure. A second maximal amplitude occurs in the dorsal blade of the dentate gyrus, there being no further change of phase. The theta activity that occurs in the presence of eserine and curare was found to have a different amplitude and phase profile from that in the freely moving rat.

Interspecies differences in the occurrence of theta

Evidence regarding the behavioral correlates of theta activity in the rat, guinea pig, rabbit, and cat is reviewed. It is suggested that the plethora of theories and the contradictions that have arisen in the interpretation of this evidence are due to the implicit assumption that there must be a correlation of theta activity with specific behaviors that will hold across species. It is concluded that this assumption is untenable and that the data indicate that there is a distinct set of theta-correlated behaviors for each species. These behaviors may correspond to important natural behaviors of the species.

Hippocampal theta rhythm. I. Depth profiles in the curarized rat

Systemic injection of curare changes the depth profile of theta rhythm seen in the hippocampus of the freely moving rat. Under curare, dorsoventral microelectrode advancement reveals the presence of a sudden phase reversal and null occurring at the level of the stratum radiatum of CA1. Further advancement reveals the presence of an amplitude peak in the vicinity of the hippocampal fissure. In addition to the change in depth profile, curare alters the relationship between the amplitudes of the two phasereversed components of the theta rhythm. The change in theta rhythm brought about by curare outlasts the paralytic effect of the drug.

Lonf-term potentiation in the dentate gyrus is preferentially induced at theta rhythm periodicity

In urethane-anesthetized rats, high frequency stimulation was applied to the medial perforant pathway at various time intervals (50, 100, 200, 350 and 500 ms) following stimulation of the same pathway by a single pulse of equal intensity. Recordings of dentate gyrus granule cell evoked responses were made to investigate the range of stimuli that are effective in inducing long-term potentiation (LTP). LTP was induced almost exclusively at the 200 ms interval, corresponding to the periodicity of the theta rhythm. Taken in conjunction with similar findings reported in the CA1 field of the hippocampal slice, these results suggest that the correlation between theta rhythm periodicity and LTP is a general phenomenon within the hippocampal formation and lends further support to the hypothesis that the naturally occurring theta rhythm may play a modulatory role in the induction of LTP.

Hippocampal theta rhythm. II. Depth profiles in the freely moving rabbit.

Depth profiles of hippocampal theta rhythm were investigated in the freely moving rabbit during three behavioral conditions: REM sleep, voluntary movement, and during sensory stimulation applied to the motionless animal. Profiles were found to be the same in all three conditions. Dorsoventral microelectrode penetration of the dorsal hippocampus revealed an approximately uniform amplitude of theta rhythm in strata oriens and pyramidal of CA1. Further microelectrode advancement revealed a sharp reversal of phase and a coincident null in amplitude in the proximal stratum radiatum. There was also a peak of theta rhythm amplitude which occurred in the molecular layer of the dorsal blade of the dentate gyrus. These data imply that in the rabbit, as in the freely moving rat, there are two generators of theta rhythm in the dorsal hippocampus, one in the dentate gyrus and the other in the overlying CA1 layer. The data also indicate the existence of a species difference in generating systems between the rabbit and the rat.

The biology and function of rapid eye movement sleep.

Rapid eye movement sleep, a stage of sleep that appears to be present in all marsupial and terrestrial placental mammals, was first identified in 1953. Although the brainstem mechanisms responsible for its generation have been clarified, the function of rapid eye movement sleep remains elusive. Recent findings suggest a role in memory processing.

Topographic Patterns of Hippocampal Theta Rhythm in Freely Moving Rat and Rabbit

In 1954 Green and Arduini (13) reported the presence of approximately sinusoidal, high-amplitude, slow waves of 3–7 cps in the hippocampus of both curarized and freely moving rabbits. In the curarized rabbit, the slow waves appeared in response to natural sensory stimulation of electrical stimulation of certain subcortical structures. The waves appeared in the freely moving animal when it was alert and interested in its surroundings. The hippocampal slow waves were termed theta rhythm in keeping with the designation that had previously been established for human EEG components in the 4–7 cps frequency range, and the theta rhythm was characterized as an arousal reaction of the hippocampus.

Influence of neurons of the parafascicular region on neuronal transmission from perforant pathway through dentate gyrus.

We have previously reported that activation of an ascending brainstem pathway by stimulation of the median raphe nucleus (MR) influences neuronal transmission from the perforant pathway through the dentate gyrus in a behaviorally dependent manner. In particular, stimulation of the MR markedly facilitated such transmission when applied during slow-wave sleep (SWS), but was ineffective when applied during the still-alert state (SAL). We present here evidence for a relay in this circuit located rostral to the MR in cells proximal to the fasciculus retroflexus (PF, parafascicular region). In contrast to stimulation of the MR, stimulation of the PF facilitates neuronal transmission from the perforant pathway through the dentate gyrus during both SWS and SAL indicating the presence of a gate at or proximal to the PF that is preferentially closed during SAL.

Reticular formation influence on neuronal transmission from perforant pathway through dentate gyrus

Electrical stimulation of the perforant pathway discharges granule cell synchronously, giving rise to a characteristic evoked potential in the granule cell layer termed here the evoked action potential or EAP. In freely moving rats, we applied 3 pulses of low intensity electrical stimulation to the medullary reticular formation prior to the application of the perforant path pulse. The effect of prior reticular formation stimulation was a marked augmentation of the normal EAP response to the perforant path stimulus. The augmentation was dependent on the behavioral state of the experimental animal (it occurred during slow-wave sleep but not during still, alert behavior) and was eliminated by anesthetic agents. The latency of EAP augmentation effect (minimum effective time interval between application of the reticular formation stimulus and the perforant path pulse) was 13--18 msec. In order to localize the sites in the medullary reticular formation from which EAP augmentation could be elicited, threshold currents for producing the effect were determined during dorso-ventral penetrations of a reticular formation stimulating electrode. EAP augmentation was elicited at low stimulus currents from a relatively broad region of the reticular formation. It was also noted that reticular formation stimulation which produced EAP augmentation always elicited one or more motor responses of the neck, back, face or vibrissae. Subsequent investigation of the pathways underlying these motor responses suggested that the effect of reticular formation stimulation on granule cell excitability was mediated by a polysynaptic pathway, the first segment of which was a projection to cells of nucleus gigantocellularis of the caudal medulla.