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

Nested hippocampal oscillations in the rodent gives rise to temporal coding that may underlie learning, memory, and decision making. Theta/gamma coupling in rodent CA1 occurs during exploration and sharp-wave ripples during quiescence. Whether these oscillatory regimes extend to primates is less clear. We therefore sought to identify correspondences in frequency bands, nesting, and behavioral coupling taken from macaque hippocampus. We found that, in contrast to the rodent, theta and gamma frequency bands in macaque CA1 were segregated by behavioral states. Beta/gamma (15-70Hz) had greater power during visual search while theta (7-10 Hz) dominated during quiescence. Moreover, delta/theta (3-8 Hz) amplitude was strongest when beta2/slow gamma (20-35 Hz) amplitude was weakest, though the low frequencies coupled with higher, ripple frequencies (60-150 Hz). The distribution of spike-field coherence revealed three peaks matching the 3-10 Hz, 20-30 Hz and 60-150 Hz bands; however, the low frequency effects were primarily due to 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. These findings diverge from the rodent oscillatory canon and call for a shift in focus and frequency when considering the primate hippocampus.

Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices

Behavioral flexibility depends on neuronal plasticity which forms and adapts the central nervous system in an experience-dependent manner. Thus, plasticity depends on interactions between the organism and its environment. A key experimental paradigm for studying this concept is the exposure of rodents to an enriched environment (EE), followed by studying differences to control animals kept under standard conditions (SC). While multiple changes induced by EE have been found at the cellular-molecular and cognitive-behavioral levels, little is known about EE-dependent alterations at the intermediate level of network activity. We, therefore, studied spontaneous network activity in hippocampal slices from mice which had previously experienced EE for 10–15 days. Compared to control animals from standard conditions (SC) and mice with enhanced motor activity (MC) we found several differences in sharp wave-ripple complexes (SPW-R), a memory-related activity pattern. Sharp wave amplitude, unit firing during sharp waves, and the number of superimposed ripple cycles were increased in tissue from the EE group. On the other hand, spiking precision with respect to the ripple oscillations was reduced. Recordings from single pyramidal cells revealed a reduction in synaptic inhibition during SPW-R together with a reduced inhibition-excitation ratio. The number of inhibitory neurons, including parvalbumin-positive interneurons, was unchanged. Altered activation or efficacy of synaptic inhibition may thus underlie changes in memory-related network activity patterns which, in turn, may be important for the cognitive-behavioral effects of EE exposure.

Awake ripples enhance emotional memory encoding in the human brain

Intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task reveal increased awake sharp-wave/ripples (aSWR) after encoding of emotional compared to neutral stimuli. Further, post-encoding aSWR-locked memory reinstatement in the amygdala and the hippocampus was predictive of later memory discrimination. These findings provide electrophysiological evidence that post-encoding aSWRs enhance memory for emotional events.

E-Cannula reveals anatomical diversity in sharp-wave ripples as a driver for the recruitment of distinct hippocampal assemblies

The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on in vivo hippocampal activity dynamics has mostly relied on single modalities such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. This technical difficulty greatly impedes multi-level investigations into network state-related changes in cellular activity. To overcome these limitations, we developed the E-Cannula integrating fully transparent graphene microelectrodes with imaging-cannula. The E-Cannula enables the simultaneous electrical recording and two-photon calcium imaging from the exact same population of neurons across an anatomically extended region of the mouse hippocampal CA1 stably across several days. These large-scale simultaneous optical and electrical recordings showed that local hippocampal sharp wave ripples (SWRs) are associated with synchronous calcium events involving large neural populations in CA1. We show that SWRs exhibit spatiotemporal wave patterns along multiple axes in 2D space with different spatial extents (local or global) and temporal propagation modes (stationary or travelling). Notably, distinct SWR wave patterns were associated with, and decoded from, the selective recruitment of orthogonal CA1 cell assemblies. These results suggest that the diversity in the anatomical progression of SWRs may serve as a mechanism for the selective activation of the unique hippocampal cell assemblies extensively implicated in the encoding of distinct memories. Through these results we demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components such as green lenses, fibers or prisms enabling the multi-modal investigation of cross-time scale population-level neural dynamics across brain regions.