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Long-term potentiation (LTP) is a candidate synaptic mechanism underlying learning and memory that has been studied extensively at the cellular and molecular level in laboratory animals. To date, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. Inquiry into the functional significance of LTP has been hindered by the absence of a human model. Here we give the first demonstration that the rapid repetitive presentation of a visual checkerboard (a photic 'tetanus') leads to a persistent enhancement of one of the early components of the visual evoked potential in normal humans. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield and is limited to one component of the visual evoked response (the N1b). The selective potentiation of only the N1b component makes overall brain excitability changes unlikely and suggests that the effect is due instead to an LTP process. While LTP is known to exist in the human brain, the ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders.

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Hippocampal rhythmical slow activity (RSA, theta) was elicited in urethanized rats by high-frequency stimulation in the reticular formation. The effects of procaine infusion (0.5 microliters, 20% wt/vol) at various loci in the ascending system from pontine reticular formation to the medial septum/diagonal band area were investigated. It was found that procaine injected at points in the ascending system anterior to the supramammillary nucleus, in the region of the medial forebrain bundle or in the medial septum, reduced the amplitude of reticularly elicited RSA but had no effect on its frequency. Procaine injected at points in the ascending system from just anterior to the reticular formation stimulation site, up to, and including the supramammillary nucleus, reduced both the frequency and amplitude of reticularly elicited RSA. These results indicate that the frequency of reticularly elicited RSA is encoded in the supramammillary area, rather than in the medial septum/diagonal band as have previously been suggested.

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Single-unit discharge was recorded from cells in the posterior hypothalamic nucleus (PH), supramammillary nucleus (SuM), and medial mammillary nucleus (MM) during hippocampal theta () elicited by stimulation of the reticular nucleus pontis oralis (RPO). In agreement with previously published work, -related cells in the PH (12 cells) were all classified as tonic -ON (increased tonic discharge rate during hippocampal ), whereas those in the SuM (9 cells) and MM (15 cells) were all classified as phasic -ON (rhythmic discharge, in phase with ongoing ). The effect of RPO stimulation on cell discharge was tested after hippocampal was abolished by infusion of procaine into the medial septum/vertical limb of the diagonal band. The RPOelicited discharge patterns of all PH tonic -ON cells and all SuM phasic -ON cells survived septal procaine infusion. Further, the discharge rate of PH cells and the frequency of burst discharge of SuM cells during RPO stimulation both increased after the infusion. In contrast, septal procaine infusion abolished the RPO-elicited rhythmic discharge pattern in MM phasic -ON cells and attenuated their discharge rates. These results indicate that the PH and SuM form parts of an ascending system mediating hippocampal , whereas the MM receives (and perhaps relays to other parts of the limbic system) rhythmic input descending from the septo-hippocampal system. In addition, PH and SuM receive descending inputs that limit the discharge rates of their -related cells during hippocampal .

Long-term potentiation (LTP) is a synaptic mechanism underlying learning and memory that has been studied extensively in laboratory animals. The study of LTP recently has been extended into humans using repetitive sensory stimulation to induce cortical LTP. In this review paper we will discuss past results from our group demonstrating that repetitive sensory stimulation (visual or auditory) induces LTP within the sensory cortex (visual/auditory, respectively) and can be measured non-invasively using EEG or fMRI. We will discuss a number of studies that indicate that this form of LTP shares several characteristics with the synaptic LTP described in animals: it is frequency dependent, long-lasting (>1 hour), input specific, depotentiates with low-frequency stimulation, and is blocked by NMDA receptor blockers in rats. In this paper we also present new data regarding the behavioral significance of human sensory LTP. These advances will permit enquiry into the functional significance of LTP that has been hindered by the absence of a human model. The ability to elicit LTP using a natural sensory stimulus non-invasively will provide a model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the diagnosis and assessment of neuropsychiatric and neurocognitive disorders.