Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density

Clinical populations have memory deficits linked to sleep oscillations that can potentially be treated with sleep medications. Eszopiclone and zolpidem (two non-benzodiazepine hypnotics) both enhance sleep spindles. Zolpidem improved sleep-dependent memory consolidation in humans, but eszopiclone did not. These divergent results may reflect that the two drugs have different effects on hippocampal ripple oscillations, which correspond to the reactivation of neuronal ensembles that represent previous waking activity and contribute to memory consolidation. We used extracellular recordings in the CA1 region of rats and systemic dosing of eszopiclone and zolpidem to test the hypothesis that these two drugs differentially affect hippocampal ripples and spike activity. We report evidence that eszopiclone makes ripples sparser, while zolpidem increases ripple density. In addition, eszopiclone led to a drastic decrease in spike firing, both in putative pyramidal cells and interneurons, while zolpidem did not substantially alter spiking. These results provide an explanation of the different effects of eszopiclone and zolpidem on memory in human studies and suggest that sleep medications can be used to regulate hippocampal ripple oscillations, which are causally linked to sleep-dependent memory consolidation.

Neural correlates of vocal initiation in the VTA/SNc of juvenile male zebra finches

Initiation and execution of complex learned vocalizations such as human speech and birdsong depend on multiple brain circuits. In songbirds, neurons in the motor cortices and basal ganglia circuitry exhibit preparatory activity before initiation of song, and that activity is thought to play an important role in successful song performance. However, it remains unknown where a start signal for song is represented in the brain and how such a signal would lead to appropriate vocal initiation. To test whether neurons in the midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) show activity related to song initiation, we carried out extracellular recordings of VTA/SNc single units in singing juvenile male zebra finches. We found that a subset of VTA/SNc units exhibit phasic activity precisely time-locked to the onset of the song bout, and that the activity occurred specifically at the beginning of song. These findings suggest that phasic activity in the VTA/SNc represents a start signal that triggers song vocalization.

Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.

Voltage Distributions in Extracellular Brain Recordings

Extracellular recordings of brain voltage signals have many uses, including the identification of spikes and the characterization of brain states via analysis of local field potential (LFP) or EEG recordings. Though the factors underlying the generation of these signals are time-varying and complex, their analysis may be facilitated by an understanding of their statistical properties. To this end, we analyzed the voltage distributions of high-pass extracellular recordings from a variety of structures, including cortex, thalamus and hippocampus, in monkeys, cats and rodents. We additionally investigated LFP signals in these recordings as well as human EEG signals obtained during different sleep stages. In all cases, the distributions were accurately described by a Gaussian within ± 1.5 standard deviations from zero. Outside these limits, voltages tended to be distributed exponentially, i.e. they fell off linearly on log-linear frequency plots, with variable heights and slopes. A possible explanation for this is that sporadically and independently occurring events with individual Gaussian size distributions can sum to produce approximately exponential distributions. For the high-pass recordings, a second explanation results from a model of the noisy behaviour of ion channels which produce action potentials via Hodgkin-Huxley kinetics. The distributions produced by this model, relative to the averaged potential, were also Gaussian with approximately exponential flanks. The model also predicted time-varying noise distributions during action potentials, which were observed in the extracellular spike signals. These findings suggest a principled method for detecting spikes in high-pass recordings and transient events in LFP and EEG signals.

Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

Behavioral studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions; however, anatomical evidence suggests that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioral-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a boundary. Combining in vivo optopatch-clamp and extracellular recordings of spontaneous and evoked sensory activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the spontaneous activity, due to particular corticostriatal connectivity and local attributes of each region. Additionally, we show differences in slow and fast oscillations and in the electrophysiological properties between striatonigral and striatopallidal neurons. In summary, these results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.

Examinations of Bilateral Epileptiform Activities in Hippocampal Slices Obtained From Young Mice

Bilateral interconnections through the hippocampal commissure play important roles in synchronizing or spreading hippocampal seizure activities. Intact hippocampi or bilateral hippocampal slices have been isolated from neonatal or immature rats (6–7 or 12–21 days old, respectively) and the mechanisms underlying the bilateral synchrony of hippocampal epileptiform activities have been investigated. However, the feasibility of examining bilateral epileptiform activities of more developed hippocampal circuitry in vitro remains to be explored. For this, we prepared bilateral hippocampal slices from C57 black mice, a strain commonly used in neuroscience and for genetic/molecular modifications. Young mice (21–24-day-old) were used in most experiments. A 600-μm-thick slice was obtained from each mouse by horizontal vibratome sectioning. Bilateral dorsal hippocampal and connecting dorsal hippocampal commissure (DHC) tissues were preserved in the slice and extrahippocampal tissues were removed. Slices were recorded in a submerged chamber mainly at a room temperature (21–22°C). Bilateral CA3 areas were monitored by extracellular recordings, and unilateral electrical stimulation was used to elicit CA3 synaptic field potentials. The unilateral stimulation could elicit population spikes in the contralateral CA3 area. These contralateral spikes were attenuated by inhibiting synaptic transmission with cobalt-containing medium and were abolished when a cut was made at the DHC. Self-sustained and bilaterally correlated epileptiform potentials were observed following application of 4-aminopyradine and became independent after the DHC cut. Bilateral hippocampal activities were detectable in some slices of adult mice and/or at 35–36°C, but with smaller amplitudes and variable waveforms compared to those observed from slices of young mice and at the room temperature. Together, these observations suggested that examining bilateral epileptiform activities in hippocampal slices of young mice is feasible. The weaknesses and limitations of this preparation and our experimentation are discussed.

ION-Decoding: A Single-channel Interactive Offline Neural Decoding Algorithm for a large number of neurons

Researchers have widely used extracellular recordings as a technique of paramount importance due to its wide usage in cognitive studies, health technologies, and prosthetics and orthotics research. To extract the required information from this technique, a critical and crucial step, called spike sorting, must be performed on the recorded signal. By this method, it is possible to analyze a single neuron (single-unit activity) and investigate its specifications, such as the firing rates and the number of action potentials (spikes) of an individual neuron. Here we introduce a novel idea of a user-friendly interactive, offline, and unsupervised algorithm called ION-Decoding. This platform extracts and aligns the spikes using a high-resolution alignment method, and the clusters can be atomically identified and manually edited. The entire procedure is performed using the minimum number of adjustable parameters, and cluster merging was performed in a smart, intuitive way. The ION-Decoding algorithm was evaluated by a benchmark dataset, including 95 simulations of two to twenty neurons from 10 minutes simulated extracellular recordings. There was not any significant relationship between the number of missed clusters with the quality of the signal (i.e., the signal-to-noise ratio (SNR)) by controlling the number of neurons in each signal (p_value=0.103). Moreover, the number of extra clusters was not significantly dependent on the parameter SNR (p_value=0.400). The accuracy of the classification method was significantly associated with the decomposability index (DI) (p_value<0.001). A number of 77% of the neurons with the DI higher than 20 had the classification accuracy higher than 80%. The ION-Decoding algorithm significantly outperformed Wave_Clus in terms of the number of hits (p_value=0.017). However, The Wave_Clus algorithm significantly outperformed the ION-Decoding algorithm when the false-positive error (FP) was considered (p_value=0.001). The ION-Decoding is thus a promising single-channel spike sorting algorithm. However, our future focuses on the improvement of the cluster representative identification and FP error reduction.

Thalamic encoding of complex sensory patterns and its possible role in cognition

The function of the higher-order sensory thalamus remains unresolved. Here, POm nucleus was examined by in vivo extracellular recordings across a range of complex sensory patterns. We found that POm was highly sensitive to multiwhisker stimuli involving complex spatiotemporal interactions. The dynamical spatiotemporal structure of sensory patterns and the different complexity of their parts were accurately reflected in precise POm activity changes. Importantly, POm was also able to respond to ipsilateral stimulation and was implicated in the representation of bilateral tactile events by integrating simultaneous signals arising from both whisker pads. We found that POm nuclei are mutually connected through the cortex forming a functional POm-POm loop. We unravelled the nature and content of the messages travelling through this loop showing that they were ‘structured patterns of sustained activity’. These structured messages were transmitted preserving their integrated structure. The implication of different cortical areas was investigated revealing that S1 plays a protagonist role in this functional loop. Our results also demonstrated different laminar implication in the processing of sustained activity in this cortical area and its transmission between hemispheres. We propose a theoretical model in which these ‘structured patterns of sustained activity’ generated by POm may play important roles in perceptual, motor and cognitive functions. From a functional perspective, this proposal, supported by the results described here, provides a novel theoretical framework to understand the implication of the thalamus in cognition. In addition, a profound difference was found between VPM and POm functioning. The hypothesis of Complementary Components is proposed here to explain it.HighlightsPOm is implicated in the representation of complex sensory patterns.POm is implicated in the encoding of bilateral tactile events.POm nuclei are mutually connected through the cortex forming a functional POm-POm loop.‘Structured patterns of sustained activity’ travelling through the loopAbstract Figure