scholarly journals Theta-burst microstimulation in the human entorhinal area improves memory specificity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ali S Titiz ◽  
Michael R H Hill ◽  
Emily A Mankin ◽  
Zahra M Aghajan ◽  
Dawn Eliashiv ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Episodic Memory ◽  
Recognition Task ◽  
Human Memory ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Memory Specificity ◽  
Neurosurgical Patients ◽  
Entorhinal Area ◽  
Theta Burst

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

scholarly journals Author response: Theta-burst microstimulation in the human entorhinal area improves memory specificity

2017 ◽  
Author(s):  
Ali S Titiz ◽  
Michael R H Hill ◽  
Emily A Mankin ◽  
Zahra M Aghajan ◽  
Dawn Eliashiv ◽  
...  
Keyword(s):  
Author Response ◽  
Memory Specificity ◽  
Entorhinal Area ◽  
Theta Burst

Effects of aging on axon terminals in the dentate molecular layer

1987 ◽  
Vol 45 ◽  
pp. 928-929
Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova
Keyword(s):  
Granule Cells ◽  
Molecular Layer ◽  
Age Groups ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Perforant Path ◽  
Axon Terminals ◽  
Fischer 344 ◽  
Spatial Memory Deficit ◽  
Effects Of Aging

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.

Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits

2008 ◽  
Vol 86 (5) ◽  
pp. 249-256 ◽  
Author(s):  
Takashi Kubota ◽  
Itsuki Jibiki ◽  
Akira Ishikawa ◽  
Tomomi Kawamura ◽  
Sonoko Kurokawa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Negative Symptoms ◽  
Clinical Effect ◽  
Perforant Path ◽  
Hippocampal Dentate Gyrus ◽  
Extracellular Dopamine ◽  
Stimulation Of ◽  
Synaptic Responses

We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.

Computer-controlled electrical stimulation for quantitative mapping of human cortical function

2009 ◽  
Vol 110 (6) ◽  
pp. 1300-1303 ◽  
Author(s):  
Mario F. Dulay ◽  
Dona K. Murphey ◽  
Ping Sun ◽  
Yadin B. David ◽  
John H. R. Maunsell ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Detection Threshold ◽  
Electrical Current ◽  
Controlled Delivery ◽  
Cortical Mapping ◽  
Cortical Function ◽  
Quantitative Mapping ◽  
Neurosurgical Patients ◽  
Discrete Area ◽  
Computer Controlled

Cortical mapping with electrical stimulation (ES) in neurosurgical patients typically involves the manually controlled delivery of suprathreshold electrical current to a discrete area of the brain. Limited numbers of trials and imprecise current delivery methods increase the variability of the behavioral response and make it difficult to collect quantitative mapping data, which is especially important in research studies of human cortical function. To overcome these limitations, the authors developed a method for computer-controlled delivery of defined electrical current to implanted intracranial electrodes. They demonstrate that stimulation can be time locked to a behavioral task to rapidly and systematically measure the detection threshold for ES in human visual cortex over many trials. Computer-controlled ES is well suited for the systematic and quantitative study of the function of virtually any region of cerebral cortex. It may be especially useful for studying human cortical regions that are not well characterized and for verifying the presence of stimulation-evoked percepts that are difficult to objectively confirm.

scholarly journals PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pojeong Park ◽  
John Georgiou ◽  
Thomas M. Sanderson ◽  
Kwang-Hee Ko ◽  
Heather Kang ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Theta Burst Stimulation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Necessary And Sufficient ◽  
Theta Burst

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

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