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P T Huerta

Publications and source records attributed to P T Huerta.

8 recordsLinked to original sources
PubMed2000

Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons.

In humans the hippocampus is required for episodic memory, which extends into the spatial and temporal domains. Work on the rodent hippocampus has shown that NMDA receptor (NMDAR) -mediated plasticity is essential for spatial memory. Here, we have examined whether hippocampal NMDARs are also needed for temporal memory. We applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells. This paradigm requires temporal processing because the conditional and unconditional stimuli are separated by 30 s (trace). We found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Thus, NMDARs in CA1 are crucial for the formation of memories that associate events across time.

Animals↗
PubMed1997

NMDA receptor-dependent refinement of somatotopic maps.

We have examined the role of NMDA receptor-mediated neural activity in the formation of periphery-related somatosensory patterns, using genetically engineered mice. We demonstrate that ectopic expression of a transgene of an NMDAR1 splice variant rescues neonatally fatal NMDAR1 knockout (KO) mice, although the average life span varies depending on the level of the transgene expression. In NMDAR1 KO mice with "high" levels of the transgene expression, sensory periphery-related patterns were normal along both the trigeminal and dorsal column pathways. In the KO mice with "low" levels of the transgene expression, the patterns were absent in the trigeminal pathway. Our results indicate that NMDA receptor-mediated neural activity plays a critical role in pattern formation along the ascending somatosensory pathways.

Alternative Splicing↗
PubMed1996

The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.

We have produced a mouse strain in which the deletion of the NMDAR1 gene is restricted to the CA1 pyramidal cells of the hippocampus by using a new and general method that allows CA1-restricted gene knockout. The mutant mice grow into adulthood without obvious abnormalities. Adult mice lack NMDA receptor-mediated synaptic currents and long-term potentiation in the CA1 synapses and exhibit impaired spatial memory but unimpaired nonspatial learning. Our results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories.

Animals↗
PubMed1996

Preservation of spatial learning in fyn tyrosine kinase knockout mice.

Previous work has shown that knockout mice lacking the fyn tyrosine kinase gene (fyn-/-) are impaired in spatial learning. Here, we have re-examined the spatial learning of fyn-/- mutants in an open field water maze. Unlike wild-type mice, fyn-/- knockouts often floated without moving when placed in the water but could swim adequately when their hind feet were mechanically stimulated. Under these conditions, fyn-/- mice showed significant improvement over trials in locating a hidden platform. On a transfer trial, at the end of training, they spent a disproportionate amount of time swimming in the location of the previously hidden platform. These findings suggest that fyn-/- knockouts are capable of spatial learning, but suffer an impairment that compromises their ability to swim normally.

Animals↗
PubMed1996

Low-frequency stimulation at the troughs of theta-oscillation induces long-term depression of previously potentiated CA1 synapses.

1. The induction of long-term weakening of synaptic transmission in rat hippocampal slices was examined in CA1 synapses during cholinergic modulation. 2. Bath application of the cholinergic agonist carbachol (50 microM) activated an oscillation of the local field potential in the theta-frequency range (5-12 Hz), termed theta. It was previously shown that a stimulation train of 40 single shocks (at 0.1 Hz) to the Schaffer collateral-commisural afferents, each synchronized with positive peaks of theta, caused homosynaptic long-term enhancement in CA1. Furthermore, long-term depression (LTD) was sporadically observed when the stimulation train was given at negative troughs of theta. Here we have sought to determine stable conditions for LTD induction during theta. 3. Synaptic weakening was reliably obtained, by giving 40 shocks (at 0.1 Hz) at theta-troughs, only in pathways that had been previously potentiated. This decrement, termed theta-LTD, was synapse specific because it did not occur in an independent pathway not stimulated during theta. The interval between the initial potentiating tetanus and theta-LTD induction could be as long as 90 min. 4. theta-LTD could be saturated; after consecutive episodes of theta-LTD induction, no significant further depression was obtained. Moreover, theta-LTD could be reversed by tetanic stimulation. 5. theta-LTD could prevent the induction of LTD by 600-900 pulses at 1 Hz. This suggests that the two protocols may share common mechanisms at the synaptic level. 6. We conclude that single presynaptic spikes that occur at low frequency and are properly timed to the troughs of theta may be a relevant mechanism for decreasing the strength of potentiated synapses.

Animals↗
PubMed1995

Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro.

In standard protocols, the frequency of synaptic stimulation determines whether CA1 hippocampal synapses undergo long-term potentiation or depression. Here we show that during cholinergically induced theta oscillation (theta) synaptic plasticity is greatly sensitized and can be induced by a single burst (4 pulses, 100 Hz). A burst given at the peak of theta induces homosynaptic LTP; the same burst at a trough induces homosynaptic LTD of previously potentiated synapses. Heterosynaptic LTD is produced at inactive synapses when others undergo LTP. The synaptic modifications during theta require NMDA receptors and muscarinic receptors. The enhancement is cooperative and occludes with standard LTP. These results suggest that the similar bursts observed during theta rhythm in vivo may be a natural stimulus for inducing LTP/LTD.

Animals↗
PubMed1993

Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state.

Brain cholinergic neurons are critical for memory function and their loss may contribute to memory impairment in Alzheimer's disease. One role of cholinergic neurons is to elicit an oscillatory activity called theta rhythm in the hippocampus, a brain region involved in memory processing. Theta rhythm occurs during periods of learning, but its effect on the synaptic plasticity that underlies learning remains unclear. We have studied synaptic plasticity in hippocampal slices during theta-frequency oscillations induced by a cholinergic agonist. Here we report that during these oscillations, synapses are in a state of heightened plasticity and can be modified by what would otherwise be ineffective stimulation. This heightened plasticity is sensitive to the timing of incoming stimuli with respect to the oscillatory activity. The results suggest that cholinergic systems may affect memory formation through the induction of an oscillatory state in which the requirements for synaptic plasticity are dramatically altered.

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