Whisker electromyograms signify awake and anesthetized states in mice.

The behavioral state of animals is essential information for functional recordings of neuronal activity; practically, the exact timing when animals recover from anesthesia is important information. Recordings of cortical local field potentials and dorsal neck electromyograms (EMGs), a widely used method to identify behavioral states, requires at least two recording electrodes, one of which also requires a craniotomy procedure. In the present study, recordings of whisker EMGs alone are sufficient to detect the state switch from anesthesia to awakening in head-fixed mice. This method uses a single electrode and thus is technically simple and demands a less physical burden to animals. Moreover, whisker EMGs recorded under anesthesia reflect respiratory rhythms.

Ethanol facilitates socially evoked memory recall in mice by recruiting pain-sensitive anterior cingulate cortical neurons.

Alcohol is a traditional social-bonding reinforcer; however, the neural mechanism underlying ethanol-driven social behaviors remains elusive. Here, we report that ethanol facilitates observational fear response. Observer mice exhibited stronger defensive immobility while observing cagemates that received repetitive foot shocks if the observer mice had experienced a brief priming foot shock. This enhancement was associated with an observation-induced recruitment of subsets of anterior cingulate cortex (ACC) neurons in the observer mouse that were responsive to its own pain. The vicariously activated ACC neurons projected their axons preferentially to the basolateral amygdala. Ethanol shifted the ACC neuronal balance toward inhibition, facilitated the preferential ACC neuronal recruitment during observation, and enhanced observational fear response, independent of an oxytocin signaling pathway. Furthermore, ethanol enhanced socially evoked fear response in autism model mice.

A new device for the simultaneous recording of cerebral, cardiac, and muscular electrical activity in freely moving rodents.

We present a new technique for the simultaneous capture of bioelectrical time signals from the brain and peripheral organs of freely moving rodents. The recording system integrates all systemic signals into an electrical interface board that is mounted on an animal's head for an extended period. The interface board accommodates up to 48 channels, enabling us to analyze neuronal activity patterns in multiple brain regions by comparing a variety of physiological body states over weeks and months. This technique will advance the understanding of the neurophysiological correlate of mind-body associations in health and disease.

[Memory engram of brain circuit].

How are memories stored in the brain and retrieved on demand? This is a frequently asked question. Indeed, we acquire new memories daily and remember old ones. However, how we can memorize one-time experiences is yet to be investigated. Here, we review possible mechanisms by which memories are maintained in neural networks.

Brief fear preexposure facilitates subsequent fear conditioning.

Post-traumatic stress disorder (PTSD) is an anxiety disorder that occurs following an unexpected exposure to a severe psychological event. A history of a brief trauma is reported to affect a risk for future PTSD development; however, little is known about the mechanisms by which a previous trauma exposure drives the sensitivity to a late-coming trauma. Using a mouse PTSD model, we found that a prior foot shock enhances contextual fear conditioning. This shock-induced facilitation of fear conditioning (i.e., priming effect) persisted for 7 days and was prevented by MK801, an N-methyl-D-aspartate receptor antagonist. Other types of trauma, such as forced swimming or tail pinch, did not induce a priming effect on fear conditioning. Thus, a trauma is unlikely generalized to modify the sensitivity to other traumatic experiences. The behavioral procedure employed in this study may be a useful tool to elucidate the etiology of PTSD.

Sound-induced modulation of hippocampal θ oscillations.

The mechanism of response of hippocampal neurons to a specific feature in sensory stimuli is not fully understood, although the hippocampus is well known to contribute to the formation of episodic memory in the multisensory world. Using in-vivo voltage-clamp recordings from awake mice, we found that sound pulses induced a transient increase in inhibitory, but not excitatory, conductance in hippocampal CA1 pyramidal cells. In local field potentials, sound pulses induced a phase resetting of the θ oscillations, one of the major oscillatory states of the hippocampus. Repetitive sound pulses at 7 Hz (θ rhythm) increased the θ oscillation power, an effect that was abolished by a surgical fimbria-fornix lesion. Thus, tone-induced inhibition is likely of subcortical origin. It may segment hippocampal neural processing and render temporal boundaries in continuously ongoing experiences.

Sound-induced hyperpolarization of hippocampal neurons.

The hippocampus is involved in episodic memory, which is composed of subjective experiences in the multisensory world; however, little is known about the subthreshold membrane potential responses of individual hippocampal neurons to sensory stimuli. Using in-vivo whole-cell patch-clamp recordings from hippocampal CA1 neurons in awake mice, we found that almost all hippocampal neurons exhibited a hyperpolarization of 1-2 mV immediately after the onset of a sound. This large-scale hyperpolarization was unaffected by the duration or pitch of the tone. The response was abolished by general anesthesia and a surgical fimbria-fornix lesion.

Operant conditioning of synaptic and spiking activity patterns in single hippocampal neurons.

Learning is a process of plastic adaptation through which a neural circuit generates a more preferable outcome; however, at a microscopic level, little is known about how synaptic activity is patterned into a desired configuration. Here, we report that animals can generate a specific form of synaptic activity in a given neuron in the hippocampus. In awake, head-restricted mice, we applied electrical stimulation to the lateral hypothalamus, a reward-associated brain region, when whole-cell patch-clamped CA1 neurons exhibited spontaneous synaptic activity that met preset criteria. Within 15 min, the mice learned to generate frequently the excitatory synaptic input pattern that satisfied the criteria. This reinforcement learning of synaptic activity was not observed for inhibitory input patterns. When a burst unit activity pattern was conditioned in paired and nonpaired paradigms, the frequency of burst-spiking events increased and decreased, respectively. The burst reinforcement occurred in the conditioned neuron but not in other adjacent neurons; however, ripple field oscillations were concomitantly reinforced. Neural conditioning depended on activation of NMDA receptors and dopamine D1 receptors. Acutely stressed mice and depression model mice that were subjected to forced swimming failed to exhibit the neural conditioning. This learning deficit was rescued by repetitive treatment with fluoxetine, an antidepressant. Therefore, internally motivated animals are capable of routing an ongoing action potential series into a specific neural pathway of the hippocampal network.

Unbalanced excitability underlies offline reactivation of behaviorally activated neurons.

Hippocampal sharp waves (SWs)/ripples represent the reactivation of neurons involved in recently acquired memory and are crucial for memory consolidation. By labeling active cells with fluorescent protein under the control of an immediate-early gene promoter, we found that neurons that had been activated while mice explored a novel environment were preferentially reactivated during spontaneous SWs in hippocampal slices in vitro. During SWs, the reactivated neurons received strong excitatory synaptic inputs as opposed to a globally tuned network balance between excitation and inhibition.

Normal learning ability of mice with a surgically exposed hippocampus.

In rats and mice, the hippocampus lies beneath higher than 1 mm of the neocortex. This anatomical feature makes it difficult to experimentally access the hippocampus from the surface of the brain in vivo. This problem may be solved by surgical removal of the cortical tissue above the hippocampus; however, it has not been examined whether this 'hippocampal window' surgery preserves the normal hippocampal function. We bilaterally aspirated the posterior parietal cortex above the dorsal hippocampus of adult male mice. These mice still exhibited normal local field potentials of the hippocampus, normal motor activity, and normal cognitive ability in the water-maze test and contextual fear conditioning, compared with intact or sham-operated controls. Thus, exposed hippocampal preparations provide a useful experimental model to study the physiology of the hippocampus.