A protocol to investigate neural coupling of brain oscillations in rodents using in vivo electrophysiological recordings.

Memory processes are highly dependent on a cross-talk between brain regions via synchronized neural oscillations. Here, we present a protocol to perform multi-site electrophysiological recordings in vivo in freely moving rodents to investigate functional connectivity across brain regions during memory processes. We describe steps for recording local field potentials (LFPs) during behavior, extracting LFP bands, and analyzing synchronized LFP activity across brain regions. This technique also provides the potential to simultaneously assess single unit activity using tetrodes. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Theta coupling within the medial prefrontal cortex regulates fear extinction and renewal.

Fear learning, and its extinction, are fundamental learning processes that allow for a response adaptation to aversive events and threats in the environment. Thus, it is critical to understand the neural mechanism that underpins fear learning and its relapse following extinction. The neural dynamics within the subregions of the medial prefrontal cortex, including the prelimbic cortex (PL) and the infralimbic (IL) cortex, and functional connectivity between them during fear extinction and its relapse, are not well understood. Using in-vivo electrophysiological recordings in awake behaving rats, we identified increased theta activity in the PL during fear learning and in the IL following extinction. Importantly, the PL-IL theta coupling is significantly enhanced throughout fear learning and extinction, but not in fear relapse. Together, our results provide evidence for the importance of synchronized PL-IL activity to regulate context-dependent retrieval of a fear extinction memory.

Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination.

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.

Single-unit activity of the anterior Globus pallidus internus in Tourette patients and posterior Globus pallidus internus in dystonic patients.

OBJECTIVES: Our goal was to provide a detailed analysis of neurons' electrophysiological activity recorded in sub-territories of Globus pallidus internus (GPi) used as Deep Brain Stimulation (DBS) targets for these clinical conditions to potentially assist electrode targeting. METHODS: We used intra-operative microelectrode recording during stereotactic neurosurgery to guide implantation of DBS lead. RESULTS: Units in the medial anterior part of GPi of 7 Tourette's syndrome patients under general anesthesia were firing at mean and median rate of 32.1 and 21 Hz respectively (n = 101), with 45% of spikes fired during bursts and 21.3 bursts per minute. In the latero-posterior part of GPi of 7 dystonic patients under local anesthesia the mean and median activity were 46.1 and 30.6 Hz respectively (n = 27), and a mean of 21.7 bursts per minute was observed, with 30% of all spikes occurring during these bursts. CONCLUSION: Units activity pattern - slow-regular, fast-irregular or fast-regular were present in different proportions between the two targets. SIGNIFICANCE: The electrophysiological characteristics of the medial-anterior part of GPi and its latero-posterior portion can be used to assist DBS electrode targeting and also support the refinement of pathophysiological models of Tourette's syndrome and Dystonia.

Auditory Tones and Foot-Shock Recapitulate Spontaneous Sub-Threshold Activity in Basolateral Amygdala Principal Neurons and Interneurons.

In quiescent states such as anesthesia and slow wave sleep, cortical networks show slow rhythmic synchronized activity. In sensory cortices this rhythmic activity shows a stereotypical pattern that is recapitulated by stimulation of the appropriate sensory modality. The amygdala receives sensory input from a variety of sources, and in anesthetized animals, neurons in the basolateral amygdala (BLA) show slow rhythmic synchronized activity. Extracellular field potential recordings show that these oscillations are synchronized with sensory cortex and the thalamus, with both the thalamus and cortex leading the BLA. Using whole-cell recording in vivo we show that the membrane potential of principal neurons spontaneously oscillates between up- and down-states. Footshock and auditory stimulation delivered during down-states evokes an up-state that fully recapitulates those occurring spontaneously. These results suggest that neurons in the BLA receive convergent input from networks of cortical neurons with slow oscillatory activity and that somatosensory and auditory stimulation can trigger activity in these same networks.

Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus.

The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and is thought to be important for the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN in gait control is not understood. Using extracellular single-unit recordings in awake patients, we found that neurons in the PPN discharged as synchronous functional networks whose activity was phase locked to alpha oscillations. Neurons in the PPN responded to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. Our results indicate that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in Parkinson's disease may result from disrupted network activity in the PPN.