Local field potential (LFP) oscillations are primarily shaped by the superposition of postsynaptic currents. Hippocampal LFP oscillations in the 25- to 50-Hz range (“slow γ”) are proposed to support memory retrieval independent of other frequencies. However, θ harmonics extend up to 48 Hz, necessitating a study to determine whether these oscillations are fundamentally the same. We compared the spectral analysis methods of wavelet, ensemble empirical-mode decomposition (EEMD), and Fourier transform. EEMD, as previously applied, failed to account for the θ harmonics. Depending on analytical parameters selected, wavelet may convolve over high-order θ harmonics due to the variable time-frequency atoms, creating the appearance of a broad 25- to 50-Hz rhythm. As an illustration of this issue, wavelet and EEMD depicted slow γ in a synthetic dataset that only contained θ and its harmonics. Oscillatory transience cannot explain the difference in approaches as Fourier decomposition identifies ripples triggered to epochs of high-power, 120- to 250-Hz events. When Fourier is applied to high power, 25- to 50-Hz events, only θ harmonics are resolved. This analysis challenges the identification of the slow γ rhythm as a unique fundamental hippocampal oscillation. While there may be instances in which slow γ is present in the rat hippocampus, the analysis presented here shows that unless care is exerted in the application of EEMD and wavelet techniques, the results may be misleading, in this case misrepresenting θ harmonics. Moreover, it is necessary to reconsider the characteristics that define a fundamental hippocampal oscillation as well as theories based on multiple independent γ bands.

Decades of hippocampal neurophysiology research have linked the hippocampal theta rhythm to voluntary movement. A consistent observation has been a robust correlation between the amplitude (or power) and frequency of hippocampal theta and running speed. Recently, however, it has been suggested that acceleration, not running speed, is the dominating influence on theta frequency. There is an inherent interdependence among these two variables, as acceleration is the rate of change in velocity. Therefore, we investigated theta frequency and amplitude of the local-field potential recorded from the stratum pyramidale, stratum radiatum, and stratum lacunosum moleculare of the CA1 subregion, considering both speed and acceleration in tandem as animals traversed a circular task or performed continuous alternation. In male and female rats volitionally controlling their own running characteristics, we found that running speed carries nearly all of the variability in theta frequency and power, with a minute contribution from acceleration. These results contradicted a recent publication using a speedclamping task, where acceleration and movement are compelled through the use of a bottomless car (Kropff et al., 2021a). Therefore, we reanalyzed the speed-clamping data replicating a transient increase in theta frequency during acceleration. Compared with track running rats, the speed-clamped animals exhibited lower velocities and acceleration values but still showed a stronger influence of speed on theta frequency relative to acceleration. As navigation is the integration of many sensory inputs that are not necessarily linearly related, we offer caution in making absolute claims regarding hippocampal physiology from correlates garnered from a single behavioral repertoire.

Many of the foundational theoretical ideas in the field of learning and memory are traced to Donald Hebb. Examination of these ideas and their evolution suggest that Karl Lashley might have significantly influenced their development. Here, we discuss the relationship between Hebb and Lashley, and the parallels between them. Many now investigating the neurobiological basis of memory may be unaware both of Hebb's original descriptions, and the likely substantial contributions of Lashley. Many of their concerns remain with us today, and by clarifying the history we hope to strengthen the foundations of our field. This article is protected by copyright. All rights reserved.

The perirhinal cortex (PER), which is critical for associative memory and stimulus discrimination, has been described as a wall of inhibition between the neocortex and hippocampus. With advanced age, rats show deficits on PER-dependent behavioral tasks and fewer PER principal neurons are activated by stimuli, but the role of PER interneurons in these altered circuit properties in old age has not been characterized. In the present study, PER neurons were recorded while rats traversed a circular track bidirectionally in which the track was either empty or contained eight novel objects evenly spaced around the track. Putative interneurons were discriminated from principal cells based on the autocorrelogram, waveform parameters, and firing rate. While object modulation of interneuron firing was observed in both young and aged rats, PER interneurons recorded from old animals had lower firing rates compared with those from young animals. This difference could not be accounted for by differences in running speed, as the firing rates of PER interneurons did not show significant velocity modulation. Finally, in the aged rats, relative to young rats, there was a significant reduction in detected excitatory and inhibitory monosynaptic connections. Together these data suggest that with advanced age there may be reduced afferent drive from excitatory cells onto interneurons that may compromise the wall of inhibition between the hippocampus and cortex. This circuit dysfunction could erode the function of temporal lobe networks and ultimately contribute to cognitive aging.

Dopaminergic neurons of the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) exhibit spontaneous firing activity. The dopaminergic neurons in these regions have been shown to exhibit differential sensitivity to neuronal loss and psychostimulants targeting dopamine transporter. However, it remains unclear whether these regional differences scale beyond individual neuronal activity to regional neuronal networks. Here, we used live-cell calcium imaging to show that network connectivity greatly differs between SNC and VTA regions with higher incidence of hub-like neurons in the VTA. Specifically, the frequency of hub-like neurons was significantly lower in SNC than in the adjacent VTA, consistent with the interpretation of a lower network resilience to SNC neuronal loss. We tested this hypothesis, in DAT-cre/loxP-GCaMP6f mice of either sex, when activity of an individual dopaminergic neuron is suppressed, through whole-cell patch clamp electrophysiology, in either SNC or VTA networks. Neuronal loss in the SNC increased network clustering, whereas the larger number of hub-neurons in the VTA overcompensated by decreasing network clustering in the VTA. We further show that network properties are regulatable via a dopamine transporter but not a D2 receptor dependent mechanism. Our results demonstrate novel regulatory mechanisms of functional network topology in dopaminergic brain regions.