Role of Glycogenolysis in Memory and Learning: Regulation by Noradrenaline, Serotonin and ATP.

This paper reviews the role played by glycogen breakdown (glycogenolysis) and glycogen re-synthesis in memory processing in two different chick brain regions, (1) the hippocampus and (2) the avian equivalent of the mammalian cortex, the intermediate medial mesopallium (IMM). Memory processing is regulated by the neuromodulators noradrenaline and serotonin soon after training glycogen breakdown and re-synthesis. In day-old domestic chicks, memory formation is dependent on the breakdown of glycogen (glycogenolysis) at three specific times during the first 60 min after learning (around 2.

Role of the Astrocytic Na(+), K(+)-ATPase in K(+) Homeostasis in Brain: K(+) Uptake, Signaling Pathways and Substrate Utilization.

This paper describes the roles of the astrocytic Na(+), K(+)-ATPase for K(+) homeostasis in brain. After neuronal excitation it alone mediates initial cellular re-accumulation of moderately increased extracellular K(+). At higher K(+) concentrations it is assisted by the Na(+), K(+), 2Cl(-) transporter NKCC1, which is Na(+), K(+)-ATPase-dependent, since it is driven by Na(+), K(+)-ATPase-created ion gradients.

Antagonists of the Vasopressin V1 Receptor and of the β(1)-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes - but the Mechanisms Differ.

Brain edema is a serious complication in ischemic stroke because even relatively small changes in brain volume can compromise cerebral blood flow or result in compression of vital brain structures on account of the fixed volume of the rigid skull. Literature data indicate that administration of either antagonists of the V1 vasopressin (AVP) receptor or the β1-adrenergic receptor are able to reduce edema or infarct size when administered after the onset of ischemia, a key advantage for possible clinical use. The present review discusses possible mechanisms, focusing on the role of NKCC1, an astrocytic cotransporter of Na(+), K(+), 2Cl(-) and water and its activation by highly increased extracellular K(+) concentrations in the development of cytotoxic cell swelling.

Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline.

Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc), diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons.

Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick.

Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5-HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5-HT receptor antagonist methiothepin and the selective 5-HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least two different receptor subtypes.

ATP derived from astrocytes modulates memory in the chick.

Memory consolidation in a discriminative bead pecking task is modulated by endogenous adenosine triphosphate (ATP) acting at purinergic receptors in the hippocampus. Consolidation, from short- to intermediate- to long-term memory during two distinct periods following training, was blocked by the non-selective P2 purinergic receptor antagonist PPADS (pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) tetrasodium salt hydrate and the specific P2Y1 receptor antagonist MRS2179. Direct injections of the ATP agonists (ATPγS and ADPβS) potentiated memory consolidation and the effect of ADPβS was blocked by MRS2179, suggesting an important role of ATP on memory consolidation via the P2Y1 receptor in the chick hippocampus.

Rapid turnover of glycogen in memory formation.

The influence of noradrenaline acting at α(2)-AR and β(2)-ARs on the turnover of glycogen after learning has been investigated. The role of glycogen turnover in memory formation was examined using weakly-reinforced, single trial bead discrimination training in day-old domestic chickens. This study follows our previous work that focused on the need for glycogen breakdown (glycogenolysis) during learning.

Role for purinergic receptors in memory processing in young chicks.

The current study used a single trial bead discrimination task for the young chick to ascertain if inhibitors of P2 purinergic receptors would impair memory retention. Suramin and PPADS provided similar retention profiles. Loss of memory retention was evident by 60 min post-training.

α₂-Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes.

In the brain, glycogen is primarily stored in astrocytes where it is regulated by several hormones/neurotransmitters, including noradrenaline that controls glycogen breakdown (in the short term) and synthesis. Here, we have examined the adrenoceptor (AR) subtype that mediates the glycogenic effect of noradrenaline in chick primary astrocytes by the measurement of glycogen turnover (total (14) C incorporation of glucose into glycogen) following noradrenergic activation. Noradrenaline and insulin increased glycogen turnover in a concentration-dependent manner.

Role of β-adrenoceptors in glucose uptake in astrocytes using β-adrenoceptor knockout mice.

Background And Purpose: β(1) -, β(2) - and β(3) -adrenoceptors determined by functional, binding and reverse transcription polymerase chain reaction (RT-PCR) studies are present in chick astrocytes and activation of β(2) - or β(3) -adrenoceptors increase glucose uptake. The aims of the present study are to identify which β-adrenoceptor subtypes are present in mouse astrocytes, the signal transduction mechanisms involved and whether β-adrenoceptor stimulation regulates glucose uptake.

Experimental Approach: Astrocytes were prepared from four mouse strains: FVB/N, DBA/1 crossed with C57BL/6J, β(3) -adrenoceptor knockout and β(1) β(2) -adrenoceptor knockout mice.

Astrocytic adrenoceptors and learning: alpha1-adrenoceptors.

Noradrenergic receptors are expressed on both on astrocytes and neurons and noradrenergic activation of astrocytic beta(2)- and beta(3)-adrenoceptors are necessary for memory consolidation. In this paper, we marshal evidence for astrocytic alpha(1)-adrenoceptor involvement in memory consolidation. We examine the role of alpha(1)-adrenoceptors in hippocampal and mesopallial (cortical) memory processing using a discriminative avoidance task in the day-old chick.

The effect of hypoxia on the functional and structural development of the chick brain.

Decreased oxygen availability during gestation is linked with altered structural development of the brain and cognitive deficits after birth. Prehatch hypoxia can induce gross neuropathology such as brain lesions or more subtle injury including selective neuronal cell loss, white matter injury and gliosis. In the current study we used the developing chick embryo to determine whether 24h of hypoxia at different prehatch ages, embryonic day 10, 12 or 14 (E10, E12 or E14), resulted in an alteration in neuronal cell number or astrocyte density in brain areas associated with learning and memory.

Inhibition of Abeta aggregation and neurotoxicity by the 39-kDa receptor-associated protein.

Aggregation of beta-amyloid protein (Abeta) to form oligomers is considered to be a key step in generating neurotoxicity in the Alzheimer's disease brain. Agents that bind to Abeta and inhibit oligomerization have been proposed as Alzheimer's disease therapeutics. In this study, we investigated the binding of fluorescein-labeled Abeta(1-42) (FluoAbeta(1-42)) to SH-SY5Y neuroblastoma cells and examined the effect of the 39-kDa receptor-associated protein (RAP), on the Abeta cell interaction.

Ultrasound exposure of the foetal chick brain: effects on learning and memory.

Ultrasound imaging of the brain is routinely used to monitor the development and resolution of brain lesions among premature and compromised newborn human babies. However, animal studies have shown that ultrasound can cause damage to developing foetal and neonatal tissues. In this study we investigated if ultrasound of the chick brain can lead to learning and memory impairment after hatch.

Rescue of Abeta(1-42)-induced memory impairment in day-old chick by facilitation of astrocytic oxidative metabolism: implications for Alzheimer's disease.

Administration of small oligomeric beta-amyloid (Abeta)(1-42) 45 min before one-trial bead discrimination learning in day-old chicks abolishes consolidation of learning 30 min post-training (Gibbs et al. Neurobiol. Aging, in press).

What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism.

The learning process sets in motion a prolonged, reproducible, and complicated pattern of brain activation, which provides information about biochemical reactions in activated brain. Study of this pattern during one-trial aversive bead discrimination in day-old chick is facilitated by precise timing of sequential metabolic events occurring between a 10-s learning period, in which the chicks learn to associate a red bead with aversive taste, and memory consolidation, indicated by unwillingness to peck at untainted red beads while freely pecking at corresponding blue beads. Inhibition of learning by metabolic inhibitors and restoration of memory by specific substrates at specific times allow determination of specific metabolic events and their neuronal or astrocytic localization.

Astrocytes and interneurons in memory processing in the chick hippocampus: roles for G-coupled protein receptors, GABA(B) and mGluR1.

Glutamate and GABA acting at mGluR1 and GABA(B) receptors, respectively, have roles in memory processing in the hippocampus up to 35 min after bead discrimination learning in the young chick. Activation of mGluR1 receptors is important at 2.5 and 30 min after training, but modulation of these receptors between these two times has no effect on memory.

Importance of adrenergic receptors in prenatally induced cognitive impairment in the domestic chick.

In the domestic chick, mild hypoxia (24h of 14% oxygen) at two stages of embryonic development results in post-hatch memory deficiencies tested using a discriminated bead avoidance task. The nature of the memory loss depends on the gestational age at which the hypoxia occurs. Hypoxia on embryonic day 10 (E10) of a 21 day incubation results in chicks with no short-term memory 10 min after training, whereas hypoxia on day 14 (E14) results in chicks with good labile memory 30 min after training but no consolidation of memory into permanent storage (120 min).

Memory loss caused by beta-amyloid protein is rescued by a beta(3)-adrenoceptor agonist.

Accumulation of the neurotoxic beta-amyloid protein (Abeta) in the brain is a key step in the pathogenesis of Alzheimer's disease (AD). Although transgenic mouse models of AD have been developed, there is a clear need for a validated animal model of Abeta-induced amnesia which can be used for toxicity testing and drug development. Intracranial injections of Abeta(1-42) impaired memory in a single trial discriminative avoidance learning task in chicks.

Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken.

From experiments using a discriminated bead task in young chicks, we have defined when and where adrenoceptors (ARs) are involved in memory modulation. All three ARs subtypes (alpha(1)-, alpha(2)- and beta-ARs) are found in the chick brain and in regions associated with memory. Glucose and glycogen are important in the role of memory consolidation in the chick since increasing glucose levels improves memory consolidation while inhibiting glucose transporters (GLUTs) or glycogen breakdown inhibits memory consolidation.

A comparison of protocols for passive and discriminative avoidance learning tasks in the domestic chick.

A one-trial learning task, where chicks learn that a bead of a particular shape and/or colour has a bitter taste (because it has been coated in 100% methyl anthranilate, MeA) and subsequently avoids it on test, has been widely used by research groups across the world. However, there are some differences in the results reported by different research laboratories. One important difference is found when chicks are trained with a diluted bitter taste on the bead (10 or 20% MeA); memory is not consolidated and fades, lasting for different times.

Memory systems in the chick: regional and temporal control by noradrenaline.

Learning starts with the information about a situation or experience delivered to different brain areas in terms of visual, olfactory, auditory and tactile inputs. Memory processing occurs in different brain locations in a well-defined temporal sequence of physiologically based stages and biochemical cascades. Using neuropharmacological techniques in one species and a robust bead discrimination task, we have been able to chart the passage of memory from acquisition to consolidation in the chick and to dissect out the multiple roles for noradrenaline in consolidating this memory.

Astrocytic involvement in learning and memory consolidation.

Astrocytes play fundamental roles in brain function, interacting with neurons and other astrocytes, yet their role in learning is not widely recognized. This review focuses on astrocytic involvement in memory consolidation following bead discrimination learning in day-old chick and draws parallels to mammalian learning, providing strong empirical support for the conclusion that the described neuronal-astrocytic interactions are universally valid. It identifies specific mechanisms whereby astrocytes support memory consolidation.