A comparison of the muscarinic response and morphological properties of identified cells in the guinea-pig olfactory cortex in vitro

148

109

This paper examines the role of slow N-methyl-D-aspartate (NMDA) channels (deactivation -150 msec) in networks that multiplex different memories in different gamma subcycles of a low frequency them oscillation. The NMDA channels are in the synapses of recurrent collaterals and govern synaptic modification in accord with known physiological properties. Because slow NMDA channels have a time constant that spans several gamma cycles, synaptic connections will form between cells that represent different memories. This enables brain structures that have slow NMDA channels to store heteroassociative sequence information in long-term memory. Recall of this stored sequence information can be initiated by presentation of initial elements of the sequence. The remaining sequence is then recalled at a rate of one memory every gamma cycle. A new role for the NMDA channel suggested by our finding is that recall at gamma frequency works well if slow NMDA channels provide the dominant component of the EPSP at the synapse of recurrent collaterals: The slow onset of these channels and their long duration allows the firing of one memory during one gamma cycle to trigger the next memory during the subsequent gamma cycle. An interesting feature of the readout mechanism is that the activation of a given memory is due to cumulative input from multiple previous memories in the stored sequence, not just 1Corresponding author. the previous one. The network thus stores sequence information in a doubly redundant way: Activation of a memory depends on the strength of synaptic inputs from multiple cells of multiple previous memories. The cumulative property of sequence storage has support from the psychophysical literature. Cumulative learning also provides a solution to the disambiguation problem that occurs when different sequences have a region of overlap. In a final set of simulations, we show how coupling an autoassociative network to a heteroassociative network allows the storage of episodic memories (a unique sequence of briefly occuring known items). The autoassociative network (cortex) captures the sequence in short-term memory and provides the accurate, time-compressed repetition required to drive synaptic modification in the heteroassociative network (hippocampus). This is the first mechanistically detailed model showing how known brain properties, including network oscillations, recurrent collaterals, AMPA channels, NMDA channel subtypes, the ADP, and the AHP can act together to accomplish memory storage and recall.

Section: Resultsmentioning

confidence: 99%

Theta/gamma networks with slow NMDA channels learn sequences and encode episodic memory: role of NMDA channels in recall.

Jensen¹,

Lisman²

1996

148

109

“…Pyramidal cells exhibit an after-depolarization (ADP) after spiking during cholinergic (Storm 1989;Andrade 1991;Caeser et al 1993;Libri et al 1994) or serotonergic modulation (Araneda and Andrade 1991 ). The ADP provides a ramp of excitation that builds up after a spike, within a time of 200 msec and then falls.…”

Section: After-depolarization (Adp)mentioning

confidence: 99%

“…Action potentials triggered at the time of information input to the network trigger an after-depolarization (ADP) that is intrinsic to each neuron (Lisman and Idiart 1995). An ADP of this kind has been observed in hippocampal and cortical neurons (Andrade 1991;Caeser et al 1993;Storm 1989;Libri et al 1994). The ADP has sufficient duration to trigger firing on subsequent theta cycles and thereby maintains STM.…”

Section: Introductionmentioning

confidence: 99%

Physiologically realistic formation of autoassociative memory in networks with theta/gamma oscillations: role of fast NMDA channels.

Jensen¹,

Idiart²,

Lisman³

1996

181

101

Recordings from brain regions involved in memory function show dual oscillations in which each cycle of a low-frequency theta oscillation (5-8 Hz) is subdivided into about seven subcycles by high frequency gamma oscillations (20-60 Hz). It has been proposed (Lisman and Idiart 1995) that such networks are a multiplexed short-term memory (STM) buffer that can actively maintain about seven memories, a capability of human STM. A memory is encoded by a subset of principal neurons that fire synchronously in a particular gamma subcycle. Firing is maintained by a membrane process intrinsic to each cell. We now extend this model by incorporating recurrent connections with modifiable synapses to store long-term memory (LTM). The repetition provided by STM gradually modifies synapses in a physiologically realistic way. Because different memories are active in different gamma subcycles, the formation of autoassociative LTM requires that synaptic modification depend on N-methyl-D-aspartate (NMDA) channels having a time constant of deactivation that is of the same order as the duration of a gamma subcycle (15-50 msec). Many types of NMDA channels have longer time constants (150 msec), as for instance those found in the hippocampus, but both fast and slow NMDA channels are present in 3Corresponding author.cortex. This is the first proposal for the special role of these fast NMDA channels. The STM for novel items must depend on activity-dependent changes intrinsic to neurons rather than recurrent connections, which have not developed the required selectivity. Because these intrinsic mechanisms are not error-correcting, STM will become slowly corrupted by noise. This limits the accuracy with which LTM can become encoded after a single presentation. Accurate encoding of items in LTM can be achieved by multiple presentations, provided different memory items are presented in a varied interleaved order. Our results indicate that a limited memory-capacity STM model can be integrated in the same network with a high-capacity LTM model.

“…The maintained firing that perpetuates shortterm memory is caused by an activity dependent process intrinsic to neurons, the after-depolarization (ADP) (Storm 1989;Andrade 1991;Caeser et al 1993;Libri et al 1994). The ramp-like rise of the ADP provides the timing function necessary to make each memory active in the appropriate gamma cycle.…”

Section: Introductionmentioning

confidence: 99%

Novel lists of 7 +/- 2 known items can be reliably stored in an oscillatory short-term memory network: interaction with long-term memory.

Jensen

Lisman²

1996

149

107

This paper proposes a model for the short-term memory (STM) of unique fists of known items, as, for instance, a phone number. We show that the ability to accurately store such lists in STM depends strongly on interaction with the preexisting long-term memory (LTM) for individual items (e.g., digits). We have examined this interaction in computer simulations of a network based on physiologically realistic membrane conductances, synaptic plasticity processes, and brain oscillations. In the model, seven STMs can be kept active, each in a different gamma-frequency subcycle of a theta-frequency oscillation. Each STM is maintained and timed by an activity-dependent ramping process. LTM is stored by the strength of synapses in recurrent collaterals. The presence of preexisting LTM for an item greatly enhances the ability of the network to store an item in STM. Without LTM, the precise timing required to keep cells firing within a given gamma subcycle cannot be maintained and STM is gradually degraded. With LTM, timing errors can be corrected and the accuracy and order of items is maintained. This attractor property of STM storage is remarkable because it occurs even though there is no LTM that identifies which items are on the list or their order. Multiple known items can be stored in STM, even though their representation is 1Corresponding author.overlapping. However, multiple, identical memories cannot be stored in STM, consistent with the psychophysical demonstration of repetition blindness. Our results indicate that meaningful computation (memory completion) can occur in the millisecond range during an individual gamma cycle.