Juan-Carlos Toledo-Salas,  Ph.D.

Research ideas

Penile erection

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In rats penile erections can be measured by just registering pressure from the corpus spongiosum of  the penis with a DSI blood pressure telemetric device. This also allows the measurement of micturition.

Using glass micro-pipettes with carbon fibers or Pontamine Sky blue electrical stimulation or the registration of neuronal single unit activity can be done to evoke penile erections or record nuclei involved in generation of penile erection. Using these methods, penile erection was evoked by electrical stimulation of various nucleus like the PVN, the septal nuclei, the laterodorsal tegmental nuclei, as well as the recording of single unit activity during spontaneous penile erections.

The questions that remain are:

Is that single unit activity really related to penile erection? In those cases penile erection was spontaneous and not evoked. Neural activity will be more related to an evoked penile erection than to a spontaneous, so recording neurons after evoked penile erections should be done.

How are the different nuclei related to penile erection? There are many nucleus involved but how do they relate to each other.  The simultaneous registration of single unit activity of various nucleus during spontaneous or evoked penile erections could tell about the neural circuit of penile erection.

As penile erection also occurs during REM sleep, the experiments should also record the EEG and neck EMG of the rat. These procedures can be done in  head-restrained unanesthethized rats. In these experiments Fixed Potential Amperometry could also be used to record dopamine levels in nuclei involved in the generation of penile  erection.

There is not much interest in this scientific research area.

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Sleep and memory

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I would like to study the relationship between sleep and memory to investigate the relationship of cortical network function with the hippocampus during memory formation.

For this I would like to study sleep (by recording EEG and neck muscle EMG) and circadian rhythms with memory in male and female rodents because there are sex differences in the regulation of sleep due to hormones (Mong et al, Journal of Neuroscience 9 November 2011, 31 (45) 16107-16116). The EEG records could reflect brain cortex activity after the hippocampus processed the memory formation.

To relate the memory to sleep, the sleep patterns could be altered by the excitation of GABA by optogenetics (as done by Sakurai, et al J Neurosci. 2017 Jun 22. pii: 0245-17. doi: 10.1523/JNEUROSCI.0245-17.2017) to stop REM sleep, which could be done during or before the T-maze training. This would allow seeing if memory were related to REM sleep or SWS. An  inhibition of SWS will also inhibit REM sleep.

I would like to use T-maze to test memory in rats (as used by JT Coyle et al, Journal of Neuroscience 1 April 1985, 5 (4) 866-873) while measuring single unit activity in the CA1 area of the hippocampus during and after T-maze learning while also measuring EEG-EMG.

The recording site for single unit activity in CA1 would be found while using a stimulating electrode in CA3 to get good CA1 EPSP and then change the electrophysiology to measure single unit activity in CA1. This would allow performing hippocampus CA3-CA1 LTP at the end of the behavioral tests after CA1 single unit recording, as LTP is related to hippocampus memory storage. If this way of inserting electrode to register single unit activity in CA1 is not possible, then traditional ways could be used to record single unit activity in the CA1 area and later perform an LTP in the opposite hippocampus CA3-CA1 area.

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As there can be changes in memory in different diseases, the control rodent could be compared to test-rodents that would have received dopamine agonists and antagonists, as dopamine neural loss is related to memory loss in Alzheimer disease and dopamine has effects on sleep. In another experiments test rats could be given ketamine (rat model of schizophrenia ) or  kainic acid (epilepsy rat model ).

The EEG analysis would include not only the records of wakefulness, slow wave sleep, REM sleep, but also analysis of SWS spindles and power spectrum waves (theta, delta, alpha, etc.) before and after the memory T-maze task. I am interested in measuring regular EEG waves (like REM waves) but analyze them using Poincare Plots and sample entropy to measure the degree of rhythmic activity of these waves.

The single unit recording of neurons could be done in both brain areas since there could be differences between the right and left-brain areas. In order to get good interpretation of the results I think that the circadian time when experiment are done should be considered, making experiments at the light or dark cycle, to evaluate if there is an influence of the circadian levels on dopamine agonists/antagonists effects and the T-Maze performance could be different in light and dark periods.

Here with  Fixed Potential Amperometry or Fast Scan Cyclic Voltammetry, in other group of rats, the dopamine levels in frontal cortex, hippocampus could be measured with carbon fiber biosensors during these T-maze memory tests, to measure the relationship between brain dopamine levels and the T-maze performance.

The registration of cortex and hippocampus could tell how these structures relate to each other.