Decoding human spontaneous spiking activity in medial temporal lobe from scalp EEG.

Linking scalp electroencephalography (EEG) signals and spontaneous firing activity from deep nuclei in humans is not trivial. To examine this, we analyzed simultaneous recordings of scalp EEG and unit activity in deeply located sites recorded overnight from patients undergoing pre-surgical invasive monitoring. We focused on modeling the within-subject average unit activity of two medial temporal lobe areas: amygdala and hippocampus. Linear regression model correlates the units' average firing activity to spectral features extracted from the EEG during wakefulness or non-REM sleep. We show that changes in mean firing activity in both areas and states can be estimated from EEG (Pearson r > 0.2, p≪0.001). Region specificity was shown with respect to other areas. Both short- and long-term fluctuations in firing rates contributed to the model accuracy. This demonstrates that scalp EEG frequency modulations can predict changes in neuronal firing rates, opening a new horizon for non-invasive neurological and psychiatric interventions.

Multidimensional encoding of movement and contextual variables by rat globus pallidus neurons during a novel environment exposure task.

The basal ganglia (BG) play a critical role in a variety of functions that are essential for animal survival. Information from different cortical areas propagates through the BG in anatomically segregated circuits along the parallel direct and indirect pathways. We examined how the globus pallidus (GP), a nucleus within the indirect pathway, encodes input from the motor and cognitive domains. We chronically recorded and analyzed neuronal activity in the GP of male rats engaged in a novel environment exposure task. GP neurons displayed multidimensional responses to movement and contextual information. A model predicting single unit activity required many task-related behavioral variables, thus confirming the multidimensionality of GP neurons. In addition, populations of GP neurons, but not single units, reliably encoded the animals' locomotion speed and the environmental novelty. We posit that the GP independently processes information from different domains, effectively compresses it and collectively conveys it to successive nuclei.

Cerebellar nuclei neurons display aberrant oscillations during harmaline-induced tremor.

Essential tremor, a common, debilitating motor disorder, is thought to be caused by cerebellar malfunction. It has been shown that rhythmic Purkinje cell firing is both necessary and sufficient to induce body tremor. During tremor, cerebellar nuclei (CN) cells also display oscillatory activity. This study examined whether rhythmic activity in the CN characterizes the occurrence of body tremor, or alternatively, whether aberrant bursting activity underlies body tremor. Cerebellar nuclei activity was chronically recorded and analyzed in freely moving and in harmaline treated rats. CN neurons displayed rhythmic activity in both conditions, but the number of oscillatory neurons and the relative oscillation time were significantly higher under harmaline. The dominant frequencies of the oscillations were broadly distributed under harmaline and the likelihood that two simultaneously recorded neurons would co-oscillate and their oscillation coherence were significantly lower. It is argued that these alterations rather than neuronal rhythmicity per se underlie harmaline-induced body tremor.

Age-Dependent Degradation of Locomotion Encoding in Huntington's Disease R6/2 Model Mice.

BACKGROUND: Huntington's disease (HD) is an inherited fatal neurodegenerative disease, leading to neocortical and striatal atrophy. The commonly studied R6/2 HD transgenic mouse model displays progressive motor and cognitive deficits in parallel to major pathological changes in corticostriatal circuitry. OBJECTIVE: To study how disease progression influences striatal encoding of movement. METHODS: We chronically recorded neuronal activity in the dorsal striatum of R6/2 transgenic (Tg) mice and their age-matched nontransgenic littermate controls (WTs) during novel environment exposure, a paradigm which engages locomotion to explore the novel environment. RESULTS: Exploratory locomotion degraded with age in Tg mice as compared to WTs. We encountered fewer putative medium spiny neurons (MSNs)-striatal projection neurons, and more inhibitory interneurons-putative fast spiking interneurons (FSIs) in Tg mice as compared to WTs. MSNs from Tg mice fired less spikes in bursts without changing their firing rate, while FSIs from these mice had a lower firing rate and more of them were task-responsive as compared to WTs. Additionally, MSNs from Tg mice displayed a reduced ability to encode locomotion across age groups, likely associated with their low prevalence in Tg mice, whereas the encoding of locomotion by FSIs from Tg mice was substantially reduced solely in old Tg mice as compared to WTs. CONCLUSION: Our findings reveal an age-dependent decay in striatal information processing in transgenic mice. We propose that the ability of FSIs to compensate for the loss of MSNs by processes of recruitment and enhanced task-responsiveness diminishes with disease progression, possibly manifested in the displayed age-dependent degradation of exploratory locomotion.

Pathological tau disrupts ongoing network activity.

Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network.

Parallel processing of environmental recognition and locomotion in the mouse striatum.

Information processing in behaving animals has been the target of many studies in the striatum; however, its dynamics and complexity remain to a large extent unknown. Here, we chronically recorded neuronal populations in dorsal striatum as mice were exposed to a novel environment, a paradigm which enables the dissociation of locomotion and environmental recognition. The findings indicate that non-overlapping populations of striatal projection neurons-the medium spiny neurons-reliably encode locomotion and environmental identity, whereas two subpopulations of short-spike interneurons encode distinct information: the fast spiking interneurons preferentially encode locomotion whereas the second type of interneurons preferentially encodes environmental identity. The three neuronal subgroups used cell-type specific coding schemes. This study provides evidence for the existence of parallel processing circuits within the sensorimotor region of the striatum.