A machine learning toolbox for the analysis of sharp-wave ripples reveals common waveform features across species.

The study of sharp-wave ripples has advanced our understanding of memory function, and their alteration in neurological conditions such as epilepsy is considered a biomarker of dysfunction. Sharp-wave ripples exhibit diverse waveforms and properties that cannot be fully characterized by spectral methods alone. Here, we describe a toolbox of machine-learning models for automatic detection and analysis of these events. The machine-learning architectures, which resulted from a crowdsourced hackathon, are able to capture a wealth of ripple features recorded in the dorsal hippocampus of mice across awake and sleep conditions. When applied to data from the macaque hippocampus, these models are able to generalize detection and reveal shared properties across species. We hereby provide a user-friendly open-source toolbox for model use and extension, which can help to accelerate and standardize analysis of sharp-wave ripples, lowering the threshold for its adoption in biomedical applications.

A machine learning toolbox for the analysis of sharp-wave ripples reveal common features across species.

The study of sharp-wave ripples (SWRs) has advanced our understanding of memory function, and their alteration in neurological conditions such as epilepsy and Alzheimer's disease is considered a biomarker of dysfunction. SWRs exhibit diverse waveforms and properties that cannot be fully characterized by spectral methods alone. Here, we describe a toolbox of machine learning (ML) models for automatic detection and analysis of SWRs. The ML architectures, which resulted from a crowdsourced hackathon, are able to capture a wealth of SWR features recorded in the dorsal hippocampus of mice. When applied to data from the macaque hippocampus, these models were able to generalize detection and revealed shared SWR properties across species. We hereby provide a user-friendly open-source toolbox for model use and extension, which can help to accelerate and standardize SWR research, lowering the threshold for its adoption in biomedical applications.

Theta- and gamma-band oscillatory uncoupling in the macaque hippocampus.

Nested hippocampal oscillations in the rodent give rise to temporal dynamics that may underlie learning, memory, and decision making. Although theta/gamma coupling in rodent CA1 occurs during exploration and sharp-wave ripples emerge in quiescence, it is less clear that these oscillatory regimes extend to primates. We therefore sought to identify correspondences in frequency bands, nesting, and behavioral coupling of oscillations taken from macaque hippocampus. We found that, in contrast to rodent oscillations, theta and gamma frequency bands in macaque CA1 were segregated by behavioral states. In both stationary and freely moving designs, beta2/gamma (15-70 Hz) had greater power during visual search whereas the theta band (3-10 Hz; peak ~8 Hz) dominated during quiescence and early sleep. Moreover, theta-band amplitude was strongest when beta2/slow gamma (20-35 Hz) amplitude was weakest, instead occurring along with higher frequencies (60-150 Hz). Spike-field coherence was most frequently seen in these three bands (3-10 Hz, 20-35 Hz, and 60-150 Hz); however, the theta-band coherence was largely due to spurious coupling during sharp-wave ripples. Accordingly, no intrinsic theta spiking rhythmicity was apparent. These results support a role for beta2/slow gamma modulation in CA1 during active exploration in the primate that is decoupled from theta oscillations. The apparent difference to the rodent oscillatory canon calls for a shift in focus of frequency when considering the primate hippocampus.

Retrosplenial and Hippocampal Synchrony during Retrieval of Old Memories in Macaques.

Memory for events from the distant past relies on multiple brain regions, but little is known about the underlying neural dynamics that give rise to such abilities. We recorded neural activity in the hippocampus and retrosplenial cortex of two female rhesus macaques as they visually selected targets in year-old and newly acquired object-scene associations. Whereas hippocampal activity was unchanging with memory age, the retrosplenial cortex responded with greater magnitude alpha oscillations (10-15 Hz) and greater phase locking to memory-guided eye movements during retrieval of old events. A similar old-memory enhancement was observed in the anterior cingulate cortex but in a beta2/gamma band (28-35 Hz). In contrast, remote retrieval was associated with decreased gamma-band synchrony between the hippocampus and each neocortical area. The increasing retrosplenial alpha oscillation and decreasing hippocampocortical synchrony with memory age may signify a shift in frank memory allocation or, alternatively, changes in selection among distributed memory representations in the primate brain.SIGNIFICANCE STATEMENT Memory depends on multiple brain regions, whose involvement is thought to change with time. Here, we recorded neuronal population activity from the hippocampus and retrosplenial cortex as nonhuman primates searched for objects embedded in scenes. These memoranda were either newly presented or a year old. Remembering old material drove stronger oscillations in the retrosplenial cortex and led to a greater locking of neural activity to search movements. Remembering new material revealed stronger oscillatory synchrony between the hippocampus and retrosplenial cortex. These results suggest that with age, memories may come to rely more exclusively on neocortical oscillations for retrieval and search guidance and less on long-range coupling with the hippocampus.

A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations.

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.

GABAA receptor in the Pedunculopontine tegmental (PPT) nucleus: Effects on cardiovascular system.

BACKGROUND: The pedunculopontine tegmental (PPT) nucleus is a heterogeneous nucleus with several functions including cardiovascular regulation. The presence of GABAA receptor has been shown in the PPT. Therefore, the cardiovascular effects of this receptor were examined. METHODS: Rats were divided into: Control; Muscimol; Bicuculline (BMI); Hexamethonium (Hexa)+BMI and Atropine+BMI groups. The femoral vein and artery were cannulated for drug administration and recording of cardiovascular parameters, respectively. Muscimol (a GABAA agonist; 1.5 and 2.5nmol), BMI (a GABAA antagonist; 0.1 and 0.2nmol) were stereotaxically microinjected into the PPT. To evaluate the peripheral cardiovascular mechanisms of GABAA receptors, Hexa (a ganglionic blocker; 10mg/kg) and atropine (a muscarinic receptor antagonist; 1mg/kg) were intravenously (iv) injected before BMI (0.2nmol). The average changes of mean arterial pressure (ΔMAP), systolic blood pressure (ΔSBP) and heart rate (ΔHR) in different intervals were calculated and compared both within and between case group and control group (repeated measures ANOVA). The peak changes in each group were also calculated and compared with those of the control group (independent sample t-test). RESULTS: Both doses of BMI significantly increased ΔMAP, ΔSBP and ΔHR compared to control, while the only higher dose of muscimol significantly decreased ΔSBP. Iv injection of Hexa significantly attenuated ΔMAP, ΔSBP and ΔHR responses induced by BMI but atropine did not affect. CONCLUSIONS: Our results demonstrate that GABAA receptor of the PPT has a tonic inhibitory effect on the cardiovascular system and its peripheral effect mostly is mediated by sympathetic system.