Episodic memory declines with advancing adult age. This decline is particularly pronounced when associations between items and their contexts need to be formed. According to theories of neural communication, the precise coupling of gamma power to the phase of the theta rhythm supports associative memory formation. To investigate whether age differences in associative memory are related to compromised theta-gamma coupling, we took EEG recordings during the encoding phase of an item-context association task. Fifty-eight younger (33 females) and 55 older (24 females) adults studied pictures of objects superimposed on background scenes. In a recognition test, objects were presented on old or new backgrounds, and participants responded if they had seen (1) the object and (2) the object/scene pair. Theta-gamma coupling supported pair memory formation in both age groups. Whereas pair memory was associated with coupling closer to the peak of the theta rhythm, item-only memory was associated with a deviation in pha...

Yuqi Ren, Yang Liu, Sanduo Zheng, and Minmin Luo (see pages [1648–1665][1]) Cholinergic neurons projecting from the medial habenula (MHb) to the interpeduncular nucleus (IPN) corelease glutamate and regulate the activity of downstream neurons that regulate behaviors associated with drug

The canonical view of motor control is that distal musculature is controlled primarily by the contralateral cerebral hemisphere; unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. To distinguish between these possibilities, we serially inactivated the parietal reach region, comprising the posterior portion of medial intraparietal area, the anterior portion of V6a, and portions of the lateral occipital parietal area, in each hemisphere of 2 monkeys (23 experimental sessions, 46 injections total) to evaluate parietal reach region's contribution to the contralateral reaching deficits observed following lateralized brain lesions. Following unilateral inactivation, reach rea...

How sleep leads to offline performance gains in learning remains controversial. A use-dependent model assumes that sleep processing leading to performance gains occurs based on general cortical usage during wakefulness, whereas a learning-dependent model assumes that this processing is specific to learning. Here, we found evidence that supports a learning-dependent model in visual perceptual learning (VPL) in humans (both sexes). First, we measured the strength of spontaneous oscillations during sleep after two training conditions that required the same amount of training or visual cortical usage; one generated VPL (learning condition), while the other did not (interference condition). During a post-training nap, slow-wave activity (SWA) and sigma activity during non-rapid eye movement (NREM) sleep and theta activity during REM sleep were source localized to the early visual areas using retinotopic mapping. Inconsistent with a use-dependent model, only in the learning condition, sigma and theta activity, n...

Overlap between events can lead to interference because of a trade-off between encoding the present event and retrieving the past event. Temporal context information, “when” something occurred, a defining feature of episodic memory, can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference is unclear. Here, by identifying brain states using scalp eEEG from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification anal...

To explore whether the thalamus participates in lexical status (word vs. nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep brain stimulation lead implantation during a visually cued word- and nonword-reading aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time-locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multi-unit spiking activity, occurring shortly before and predominantly time-locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization ...

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice of both sexes while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel: an unbiased, temporally-precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for underst...

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Drosophila . Here we analyze how exposure to a novel stimulus causes override of gustatory (proboscis-extension reflex or “PER”) habituation. While brief sucrose contact with tarsal hairs causes naïve Drosophila to extend their proboscis, persistent exposure reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief...

Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here, male rats performed an attentional set-shifting task measuring intradimensional (ID) and extradimensional (ED) shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the ED shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced correct within-trial second choice responses. This evidence shows that transfer of information via the MD is critical when rapid within-trial updates in estab...

Here, we reveal an unbiased view of the brain regions that provide specific inputs to aromatase-expressing cells in the medial amygdala, neurons that play an outsized role in the production of sex-specific social behaviors, using rabies tracing and light sheet microscopy. While the downstream projections from these cells are known, the specific inputs to the aromatase-expressing cells in the medial amygdala remained unknown. We observed established connections to the medial amygdala (e.g., bed nucleus of the stria terminalis and accessory olfactory bulb) indicating that aromatase neurons are a major target cell type for efferent input including from regions associated with parenting and aggression. We also identified novel and unexpected inputs from areas involved in metabolism, fear and anxiety, and memory and cognition. These results confirm the central role of the medial amygdala in sex-specific social recognition and social behavior, and point to an expanded role for its aromatase-expressing neurons in...