Sprague-Dawley Rats Differ in Responses to Medial Perforant Path Paired Pulse and Tetanic Activation as a Function of Sex and Age.

Network plasticity in the medial perforant path (MPP) of adult (five to nine months) and aged (18-20 months) urethane-anesthetized male and female Sprague Dawley rats was characterized. Paired pulses probed recurrent networks before and after a moderate tetanic protocol. Adult females exhibited greater EPSP-spike coupling suggesting greater intrinsic excitability than adult males.

Novelty-like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress-inducing activation worsens its effects.

The earliest abnormality associated with Alzheimer's disease (AD) is the presence of persistently phosphorylated pretangle tau in locus coeruleus (LC) neurons. LC neuron numbers and fiber density are positive predictors of cognition prior to death. Using an animal model of LC pretangle tau, we ask if LC activity patterns influence the sequelae of pretangle tau.

Locus Coeruleus Optogenetic Modulation: Lessons Learned from Temporal Patterns.

After reviewing seminal studies using optogenetics to interrogate the functional role of the locus coeruleus in behavior, we conclude that differences in firing rates and firing patterns of locus coeruleus neurons contribute to locus coeruleus nucleus heterogeneity by recruiting different output circuitry, and differentially modifying behavior. The outcomes initiated by different optogenetic input activation patterns and frequencies can have opposite consequences for behavior, activate different neurons in the same target structure, be supported by distinct adrenoceptors and vary with behavioral state.

Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats.

The locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here, we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 ms or 10 s accelerated acquisition of a similar odor discrimination.

The 'a, b, c's of pretangle tau and their relation to aging and the risk of Alzheimer's Disease.

Braak has described the beginnings of Alzheimer's Disease as occurring in the locus coeruleus. Here we review these pretangle stages and relate their expression to recently described normal features of tau biology. We suggest pretangle tau depends on characteristics of locus coeruleus operation that promote tau condensates.

Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats.

In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is demonstrable at 24 h, but not 48 h, posttraining.

An experimental model of Braak's pretangle proposal for the origin of Alzheimer's disease: the role of locus coeruleus in early symptom development.

Background: The earliest brain pathology related to Alzheimer's disease (AD) is hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons. Braak characterizes five pretangle tau stages preceding AD tangles. Pretangles begin in young humans and persist in the LC while spreading from there to other neuromodulatory neurons and, later, to the cortex.

Locus Coeruleus Optogenetic Light Activation Induces Long-Term Potentiation of Perforant Path Population Spike Amplitude in Rat Dentate Gyrus.

Norepinephrine (NE) in dentate gyrus (DG) produces NE-dependent long-term potentiation (NE-LTP) of the perforant path-evoked potential population spike both and . Chemical activators infused near locus coeruleus (LC), the source of DG NE, produce a NE-LTP that is associative, i.e.

Pheromone-Induced Odor Associative Fear Learning in Rats.

Alarm pheromones alert conspecifics to the presence of danger. Can pheromone communication aid in learning specific cues? Such facilitation has an evident evolutionary advantage. We use two associative learning paradigms to test this hypothesis.

Revisiting metaplasticity: The roles of calcineurin and histone deacetylation in unlearning odor preference memory in rat pups.

Previous work has shown that 24 h duration odor preference learning, induced by one-trial training, generates a down-regulation of the GluN1 receptor in anterior piriform cortex at 3 h, and results in metaplastic unlearning if a second training trial is given at 3 h. The GluN1 receptor upregulates at 24 h so 24 h spaced training is highly effective in extending memory duration. The present study replicates the piriform cortex unlearning result in the olfactory bulb circuit and further studies the relationship between the initial training strength and its associated metaplastic effect.

Histone deacetylase inhibition induces odor preference memory extension and maintains enhanced AMPA receptor expression in the rat pup model.

Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in neonate rat pups that normally produces only 24-h memory to test behavior and examine receptor protein expression.

CaMKII mediates stimulus specificity in early odor preference learning in rats.

After naturalistic odor preference training, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was rapidly phosphorylated in the olfactory bulb, specifically in the odor encoding regions of the glomerular layer and external plexiform layer. Intrabulbar CaMKII antagonist experiments revealed that CaMKII supports short- and long-term preference memory formation. With bulbar PKA activation as the unconditioned stimulus odor preferences could be induced despite CaMKII blockade, but now odor specificity was lost, with odor preference generalizing to an untrained odor.

The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain.

Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the locus coeruleus (LC)-norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer's-related pathology appears, with most people showing at least some tau pathology by their mid-20s.

GANEing traction: The broad applicability of NE hotspots to diverse cognitive and arousal phenomena.

The GANE (glutamate amplifies noradrenergic effects) model proposes that local glutamate-norepinephrine interactions enable "winner-take-more" effects in perception and memory under arousal. A diverse range of commentaries addressed both the nature of this "hotspot" feedback mechanism and its implications in a variety of psychological domains, inspiring exciting avenues for future research.

Learning-Induced Metaplasticity? Associative Training for Early Odor Preference Learning Down-Regulates Synapse-Specific NMDA Receptors via mGluR and Calcineurin Activation.

Rat pups readily form a 24-h associative odor preference after a single trial of odor paired with intermittent stroking. Recent evidence shows that this training trial, which normally increases AMPA receptor responses in the anterior piriform cortex both 3 and 24 h following training, induces a down-regulation of NMDA receptors 3 h later followed by NMDA receptor up-regulation at 24 h. When retrained with the same odor at 3 h, rat pups unlearn the original odor preference.

Arc-Expressing Neuronal Ensembles Supporting Pattern Separation Require Adrenergic Activity in Anterior Piriform Cortex: An Exploration of Neural Constraints on Learning.

Unlabelled: Arc ensembles in adult rat olfactory bulb (OB) and anterior piriform cortex (PC) were assessed after discrimination training on highly similar odor pairs. Nonselective α- and β-adrenergic antagonists or saline were infused in the OB or anterior PC during training. OB adrenergic blockade slowed, but did not prevent, odor discrimination learning.

Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory.

Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots.

Epac activation initiates associative odor preference memories in the rat pup.

Here we examine the role of the exchange protein directly activated by cAMP (Epac) in β-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac activation produced both short-term (STM) and long-term (LTM) odor preference memories.

Learning modulation of odor representations: new findings from Arc-indexed networks.

We first review our understanding of odor representations in rodent olfactory bulb (OB) and anterior piriform cortex (APC). We then consider learning-induced representation changes. Finally we describe the perspective on network representations gained from examining Arc-indexed odor networks of awake rats.

Arc visualization of odor objects reveals experience-dependent ensemble sharpening, separation, and merging in anterior piriform cortex in adult rat.

Visualization using the immediate early gene Arc revealed sparser and more robust odor representations in the anterior piriform cortex of adult rats when odor was associated with water reward over 2-3 d. Rewarded odor "mixtures" resulted in rats responding to either component odor similarly, and, correspondingly, the odor representations became more similar as indexed by increased overlap in piriform Arc-expressing (Arc(+)) pyramidal neurons. The increased overlap was consistent with the rats' generalization from component odors.

A cognitive rehabilitation paradigm effective in male rats lacks efficacy in female rats.

Cognitive dysfunction, as a consequence of dementia, is a significant cause of morbidity lacking efficacious treatment. Females comprise at least half of this demographic but have been vastly underrepresented in preclinical studies. The current study addressed this gap by assessing the protective efficacy of physical exercise and cognitive activity on learning and memory outcomes in a rat model of vascular dementia.