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Hay, Y. A.

Publications and source records attributed to Hay, Y. A..

4 recordsLinked to original sources

Different encoding of reward location in dorsal and ventral hippocampus

Hippocampal neurons encode a cognitive map for spatial navigation1. When they fire at specific locations in the environment, they are known as place cells2. In the dorsal hippocampus place cells accumulate at current navigational goals, such as learned reward locations3-6. In the intermediate-to-ventral hippocampus (here collectively referred to as ventral hippocampus), neurons fire across larger place fields7-10 and regulate reward- seeking behavior11-16, but little is known about their involvement in reward-directed navigation. Here, we compared the encoding of learned reward locations in the dorsal and ventral hippocampus during spatial navigation. We used calcium imaging with a head- mounted microscope to track the activity of CA1 cells over multiple days during which mice learned different reward locations. In dorsal CA1 (dCA1), the overall number of active place cells increased in anticipation of reward but the recruited cells changed with the reward location. In ventral CA1 (vCA1), the activity of the same cells anticipated the reward locations. Our results support a model in which the dCA1 cognitive map incorporates a changing population of cells to encode reward proximity through increased population activity, while the vCA1 provides a reward-predictive code in the activity of a specific subpopulation of cells. Both of these location-invariant codes persisted over time, and together they provide a dual hippocampal reward-location code, assisting goal- directed navigation17, 18.

neuroscience↗

Brainstem cholinergic modulation of the thalamocortical activity in urethane anesthetized mice.

In mammals, sleep consists in the recurrence of two main stages the rapid eye movement (REM) sleep and the slow wave sleep (SWS). The full expression of sleep rhythms requires an intact thalamocortical loop, and its modulation by neuromodulators such as acetylcholine. A high tone of acetylcholine is observed during REM sleep while a low tone of acetylcholine modulates the cortical slow waves during SWS. Brainstem Cholinergic neurons activity correlates with cortical sleep stages but these neurons do not project directly to the cortex. Instead, they could contribute to cortically-recorded sleep stage modulation via a thalamic relay, in particular via the midline thalamic nuclei. Focusing on the brainstem LDTg cholinergic neurons, I investigated how midline thalamic single unit activity and cortical sleep-like stages are modulated during optogenetic-induced activation or silencing of LDTg cholinergic neurons in urethane anesthetized mice. Thalamic neurons were more active during REM-like than SWS-like stages. Bursting activity predominated during SWS-like while tonic firing was prominent during REM-like stage. Optogenetic silencing of the brainstem LDTg cholinergic neurons abolished REM-like stages and reduced tonic spiking of thalamic neurons. Moreover, during SWS-like, silent Down states were prolonged and thalamic tonic spiking during Up states was reduced. Stimulation of the brainstem LDTg cholinergic neurons had a mild effect on thalamic activity even though tonic discharge was increased. Surprisingly, optogenetic stimulation abolished as well REM-like stages maybe through compensatory mechanisms.

neuroscience↗

Cholinergic suppression of sharp wave-ripples impairs hippocampus-dependent spatial memory

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to have different functions in this process. These network states are controlled by neuromodulatory inputs, including the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice. We found that optogenetic stimulation of septal cholinergic neurons (1) impaired memory formation when activated at goal location but not during navigation; (2) reduced sharp wave-ripple (SWR) incidence at goal location; and (3) reduced SWR incidence and enhanced the-ta-gamma oscillations during sleep. These results underscore the importance of appropriate timing of cholinergic input in long-term memory formation, which might help explain the limited success of cholinesterase inhibitor drugs in treating memory impairment in Alzheimers disease.

neuroscience↗

Basal forebrain and brainstem cholinergic neurons differentially impact amygdala circuits and learning-related behavior

The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in ChAT-cre mice we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous ACh release resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of acetylcholine-mediated rhythmicity in amygdala networks. Consistent with this, in vivo NBm activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic or nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons however resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Since learning and memory is supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories.

neuroscience↗