MODULE 2 | CNS Flashcards by CHESKA CIANNELLE FRANCISCO

controls voluntary muscles

SOMATIC NS

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controls involuntary muscle

AUTONOMIC NS

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AUTONOMIC NS

arouses body to expend energy

SYMPATHETIC NS

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AUTONOMIC NS

calms body to conserve & maintain energy

PARASYMPATHETIC NS

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electrically excitable cells that process and transmit information via an electrochemical process

NEURONS

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highly branched complex “trees”
receive & integrate the input from other neurons & conduct this information to the cell body

DENDRITES

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carries the output signal of a neueron from the cell body, sometimes over long distances
only one in every neuron, but may branch distally to contact multilpe targets

AXONS

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makes contact with other neurons at specialized junctions called synapse

AXON TERMINAL

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specialized junctions/spaces
where neurotransmitter chemicals are released that interact with receptors on other neurons

SYNAPSES

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2 BROAD CATEGORIES OF NEURONAL SYSTEM IN CNS

Heirarchial system
Nonspecific / Diffuse Neuronal system

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NEURONAL SYSTEM

include all pathways directly involved in sensory perception and motor control

HIERARCHICAL SYSTEM

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NEURONAL SYSTEM | HIERARCHICAL

____ at any link incapacitates the system

lesion

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NEURONAL SYSTEM | HIERARCHICAL

in ____ system, information is processed sequentially by successive integrations at each relay nucleus on its way to the cortex

sensory system

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2 types of Hierarchical system

Relay / Projection
Local circuit

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HIERARCHICAL CELLS

relatively large axons
emit collaterals that arborize extensively in the vicinity of the neurons
excitatory
glutamate
interconnecting pathways transmit signals over long distances

RELAY / PROJECTION

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HIERARCHICAL CELLS

small axons
arborize in the immediate vicinity of the cell body
inhibitory
GABA / Glycine
recurrent feedback pathways and feed-forward pahtways

LOCAL CURCUIT

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primary inhibitory nuerotransmitter in the brain

GABA

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major excitatory transmitter

GLUTAMATE

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primary inhibitory nuerotransmitter in the spinal cord

GLYCINE

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NEURONAL SYSTEM

include the Dopamine, Serotonin, Norepenephrine, Acetylcholine
some peptide-containing pathways
small, approx 1500 on each side of the brain (rat)
axons are very fine and unmyelinated
NT: monoamines
RECEPTORS: adrenergic receptros (metabotropic, type 2)
implicated in functions such as sleeping, waking, attention, appetite, and emotional states

NONSPECIFIC / DIFFUE NERUONAL SYSTEM

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NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE

include ____, ____, ____, ____

dopamine
serotonin
norepenephrine
acetylcholine

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NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE

found in compact cell group called locus coeruleus located in the caudal pontine central gray matter

NE cell bodies

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NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE

axons are ____ & ____

very fine & unmyelinated

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NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE

neurotransmitters

monoamines

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# **NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE** receptors

adrenergic receptors | **metabotropic, type 2**

# **NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE** pathways emanating from ____

reticular formation

# **NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE** **reticular formation** is often found in the

brain stem

**CNS** always act on what channel

ion-channel

explains the **mehcanism of impulse transport** across the **synapse**

SYNAPTIC NEUROTRANSMISSION

presence of **gaps** or **spaces**

synapse

nervous system is ____

discontinuous

# **PARTS OF SYNAPSE** * synthesis, storage (vesicles), **release** or **exocytosis** of neurotransmitter * has enzymes: **metabolism** of NT * has autoreceptors: **inhibitory** effect

PRESYNAPSE

# **PARTS OF SYNAPSE** * has enzymes: **metabolism**

CLEFT

# **PARTS OF SYNAPSE** * has the **majority of receptors**: **excitatory** effect * enzymes: **metabolism**

POST SYNAPSE

**INHIBITORY** neurotransmitter

DOPAMINE GABA GLYCINE SEROTONIN

**EXCITATORY** neurotransmitter

ACETYLCHOLINE NOREPENEPHRINE GLUTAMATE

# **SYNTHESIS OF ACETYLCHOLINE** **precursor** that **must be actively transported** into neurons for **acetylcholine synthesis**

CHOLINE

# **SYNTHESIS OF ACETYLCHOLINE** transport of choline is **inhibited** by ____

hemicholinium

# **SYNTHESIS OF ACETYLCHOLINE** **Ach** binds to what receptor

muscharinic

# **SYNTHESIS OF ACETYLCHOLINE** **protects** the Ach from the **metabolism**/**degradation**

uptake into storage vesicles

# **SYNTHESIS OF ACETYLCHOLINE** the **release** of neurotrnasmitter is **blocked** by ____

botulinum toxin

# **SYNTHESIS OF ACETYLCHOLINE** causes the **release** of **Ach**

sppider venom a-latrotoxin

# **SYNTHESIS OF ACETYLCHOLINE** **spider venom** is also known as

a-latrotoxin

# **SYNTHESIS OF ACETYLCHOLINE** **postsynaptic** receptor is **activated** by ____

binding of the NT

has no **direct reuptake** to presynapse

acetylcholine

# **SYNTHESIS OF ACETYLCHOLINE** **Ach** needed to be ____ to be **uptaken** to **presynapse**

choline

# **SYNTHESIS OF ACETYLCHOLINE** **Ach** is **rapidly hydrolyzed** by ____ in the **synaptic cleft**

acetylcholinesterase

# **SYNTHESIS OF ACETYLCHOLINE** which can **enhance** Ach levels

anticholinesterases

# **SYNTHESIS OF ACETYLCHOLINE** **ion** needed for the **release** of Ach to the **cleft**

Calcium ion

# **SYNTHESIS OF ACETYLCHOLINE** **converts** acetylcholinesterase into **choline** & **acetate**

acetylcholinesterase

# **SYNTHESIS OF NOREPENEPHRINE** **NE** binds to what receptors

adrenergic

# **SYNTHESIS OF NOREPENEPHRINE** **rate limiting** step

hydroxylation of tyrosine

**END**ogenous cathecolamines

Epinephrine Norepenephrine Dopamine

# **SYNTHESIS OF NOREPENEPHRINE** **product** of **hydroxylation** of **tyrosine** | rate-limiting step

L-DOPA

# **SYNTHESIS OF NOREPENEPHRINE** **enzyme** in hydroxylation of tyrosine | conversion of tyrosine → L-DOPA

tyrosine hydroxylase

# **SYNTHESIS OF NOREPENEPHRINE** **inhibits** the enzyme **tyrosine hydroxylase**

metyrosine

# **SYNTHESIS OF NOREPENEPHRINE** sequence of kineme

tyrosine ↓ L-DOPA ↓ dopamine ↓ norepenephrine

# **SYNTHESIS OF NOREPENEPHRINE** responsible for the **transport** of the monoamine NT (**DE**) to the **vesicle**

VMAT - vesicular monoamine transporter

# **SYNTHESIS OF NOREPENEPHRINE** the **transport** of **dopamine** to the **vesilce** is **inhibited** by

reserpine

# **SYNTHESIS OF NOREPENEPHRINE** **dopamine enters the vesicle** and is **converted** to ____

norepenephrine

# **SYNTHESIS OF NOREPENEPHRINE** causes **fusion** of the **vesicles** with the cell membrane in a process known as **exocytosis**

influx of calcium

# **SYNTHESIS OF NOREPENEPHRINE** release **ENHANCERS**

**Thy**ramine **Eph**edrine **Amp**hetamine, **Ang**iotensin II **Meth**ampethamine | Tatay (THY) Efren (EPH) AMP si ANGel may METH

# **SYNTHESIS OF NOREPENEPHRINE** release **INHIBITORS**

**Gua**nadrel **Gua**nethedine **Bre**tylium

# **SYNTHESIS OF NOREPENEPHRINE** the **release** of **the** NE from the **vesicle** is a process called

exocytosis

# **SYNTHESIS OF NOREPENEPHRINE** NE is **synthesized** in the

vesicle

# **SYNTHESIS OF NOREPENEPHRINE** NE is **diffused** into ____ where **epinephrine** is synthesized

adrenal medula

# **SYNTHESIS OF NOREPENEPHRINE** what does MAO **inhibitor** do

enhances the NE levels

# **SYNTHESIS OF NOREPENEPHRINE** reuptake **INHIBITORS**

**Co**caine **Ato**moxetine **Sib**rutamine **Imip**ramine | COl mo na si ATO SIBihin mo IMIP na ako

# **SYNTHESIS OF NOREPENEPHRINE** reuptake **inhibitors** ____ the **effect** of **NE**

increases/enhances

# **SYNTHESIS OF NOREPENEPHRINE** breaks down **NE**, **SE**, **EPI**

MAO A

# **SYNTHESIS OF NOREPENEPHRINE** breaks down **DA**

MAO B

neurotransmitter that is associated with **Parkinson's disease** and **increased prolactin hormone**

DOPAMINE

**chemicals** that **take a nerve signal** across the synaptic gap beetween a sending neuron and a recieveing one

neurotransmitters

2 GROUPS OF NEUROTRANSMITTERS

1. classical 2. neuropeptide NTs

# **2 GROUPS OF NEUROTRANSMITTERS** * **small** molecule NTs * mainly **amino acids** and **amines**

CLASSICAL

# **2 GROUPS OF NEUROTRANSMITTERS** * relatively **larger** * combination of **two or more amino acids** joined by peptide bonds

NEUROPEPTIDE NTs

# **AMINO ACID NTs** * **acidic** amino acid * **excitatory**

GLUTAMATE

# **AMINO ACID NTs** * **neutral** amino acid * **inhibitory**

GLYCINE GABA

does **GLUTAMINE** have **direct** reuptake or no

no GLUTAMATE → GLUTAMINE → GLUTAMATE | enzymes: glutamine synthetase, glutaminase

# **AMINO ACID NTs** * **released** into the synaptic cleft by **Ca-dependent exocytosis** * meediates **excitatory** post synaptic transmission * vesicular glutamate transporter (VGLUT) * activates **both** **ionotropic** and **metabotropic** receptors * all are composed of **four subunits**

GLUTAMATE

# **AMINO ACID NTs | GLUTAMATE** **released** into the synaptic cleft by

Ca-dependent exocytsosis

# **AMINO ACID NTs | GLUTAMATE** mediates ____ post synaptic transmission

excitatory

# **AMINO ACID NTs | GLUTAMATE** **activates** what kind of **receptors**

both ionotropic & metabotropic

# **AMINO ACID NTs | GLUTAMATE** how many subunits

# **GLUTAMATE IONOTROPIC RECEPTORS** * **GluA1 - GluA4** subunits * **majority contain GluA2 subunit** and **permeable** to **Na** and **K** but **not** to **Ca** * **some** are **present** on **inhibitory interneurons**, **lack** the **GluA2** subunit and are also **permeable to Ca**

AMPA

# **GLUTAMATE IONOTROPIC RECEPTORS** AMPA subunits

GluA1 - A4

# **GLUTAMATE IONOTROPIC RECEPTORS** **AMP** are **permeable** to

Na & K

# **GLUTAMATE IONOTROPIC RECEPTORS** **AMP** are **not** permeable to

# **GLUTAMATE IONOTROPIC RECEPTORS** * **high levels** in the **hippocampus**, **cerebellum**, and **spinal cord** * formed from a number of subunit combinations (**GluK1-K5**) * **permeable** to **Na** and **K** and in **some subunit combinations** can also be **permeable** to **Ca**

KA (Kainate) Receptor

# **GLUTAMATE IONOTROPIC RECEPTORS** * **present** on essentially **all neurons** in the CNS * **highly permeable** to **Ca** as well as to **Na** and **K**

NMDA

# **GLUTAMATE IONOTROPIC RECEPTORS** NMDA receptor channel opening: ____ must **bind** the receptor

GLUTAMATE

# **GLUTAMATE IONOTROPIC RECEPTORS** NMDA receptor channel opening: **membrane** must be ____

depolarized

act **indirectly** on **ion channels** via G protein

G protein-coupled receptors

# **GLUTAMATE METABOTROPIC RECEPTORS** * typically located **postsynaptically** (excitatory) * **activate phospholipase C**, leading to inositol triposphate mediated intracellular Ca release

GROUP I

# **GLUTAMATE METABOTROPIC RECEPTORS** what does **Group 1** receptors **activate**

phospholipase C

# **GLUTAMATE METABOTROPIC RECEPTORS** * typically located on **presynaptic** nerve terminals and act as **inhibitory** autoreceptors * activation causes the **inhibition** of **Ca channels**, resluting in **inhibition** of **transmitter release** * are activated only when the **concentration of glutamte** rises to **high levels** during **repetitive stimulation** of the synapse * activation also causes the **inhibition of adenylyl cyclase** and **decreases cAMP generation**

GROUP II & III receptors

# **AMINO ACID NTs** **inhibitory** NTs typically released from **local interneurons**

GABA GLYCINE

# **AMINO ACID NTs** * **selectively permeable** to **Cl**

GLYCINE

# **AMINO ACID NTs | GLYCINE** ____ **selectively blocks** glycine repectors

STRYCHNINE

# **AMINO ACID NTs** * **ionotropic** receptor that are **selectively permeable** to **Cl** * mediate **fast** component of **IPSP**

GABA A

# **AMINO ACID NTs** ion channels associated with **GABA A**

chloride channels

# **AMINO ACID NTs** * **metabotropic** receptors, **selectively activated** by **Baclofen** (**GABA B agonist**) * **inhibit Ca channel** or **activate K channel** * also **inhibit adenylyl cyclase** and **decrease cAMP generation**

GABA B

# **AMINO ACID NTs** GABA B agonist

Baclofen

* **first compound** to be **identified pharmacologically** as a **transmitter** in the CNS * **responses** are **mediated** by **both muscarinic** and **nicotinic** receptors * **degraded** by **cholinesterases** * **presenile dementia** of the **Alzheimer** type is reportedly associated with a profound loss of cholinergic neurons

ACETYLCHOLINE

# **ACETYLCHOLINE** **responses** are **mediated** by what receptors

muscarinic & nicotinic

# **ACETYLCHOLINE** which has **slower** effects? NICOTNIC or MUSCARINIC

muscarinic

# **ACETYLCHOLINE** **CNS responses** are mostly mediated by ____

GPC muscarinic receptors

# **ACETYLCHOLINE** degraded by

cholinesterases

# **ACETYLCHOLINE** **8 major CNS nuclei** of **Ach neurons** have been characterizedd with ____

diffuse projections

a **target** for management of **Alzheimer's disease**

anticholinesterase

**low** acetylcholine levels

Alzheimer

what to do to **increase** the levels of **Ach**

inhibit cholinesterases

MONOAMINES

Catecholamines: DA, NE Serotonin Histamine

# **MONOAMINES** **serotonin** is also known as

5-hydroxytryptamine 5-HT

# **MONOAMINES** **Norepenephrine** is also known as

noradrenaline

# **MONOAMINES** energy **expanding**

Ergotrophic vigilance NE

# **MONOAMINES** energy **conserving**

Trophatrophic SE

# **MONOAMINES** pleasure drive

# **MONOAMINES** * most **noradrenergic** neurons are **located** in the **locus coeruleus** or the lateral tegmental area of the reticular formation * an **amine**, **excitatory** transmitter of the **brain** and **smooth muscle** * **metabotropic** * **hyperpolarizes** the neuron by **increasing potassium conductance** via the **Alpha-2 receptor** (GI - inhibitory) * enhances **excitatory** inputs in most areas of the **CNS** by both **indirect** and **direct** mechanisms * **induce** **arousal**, **heighten mood** * **impaired monoamine** has been associated with **depression**

NOREPENEPHRINE

# **MONOAMINES | NOREPENEPHRINE** most **noradrenergic neurons** are located in the

locus coeruleus

# **MONOAMINES | NOREPENEPHRINE** **excitatory** transmitter of the ____ and _____

brain & smooth muslce

# **MONOAMINES | NOREPENEPHRINE** all receptors are ____

metabotropic

# **MONOAMINES | NOREPENEPHRINE** mechanism involves **disinhibition**

indirect mechanism

# **MONOAMINES | NOREPENEPHRINE** mechanism involves **blockade** of **potassium conductance**

direct mechanism

# **MONOAMINES | NOREPENEPHRINE** **impaired monoamine** neurotransmission has been associated with ____

depression

# **MONOAMINES | NOREPENEPHRINE** drugs that **induce monoamine release** are indicated for ____ and ____

attention deficit disorder (ADHD) and narcolepsy

# **MONOAMINES** * **synthesized** from **L-dopa** * **degraded** by **monoamine oxidase A** in the **brain** and **MAO B outside the CNS** by **catechol-O-methyl transferase (COMT)** * receptors are all **metabotropic** * major pathways are the projection linking the **substantia nigra to the neostriatum** and the projection linking the **ventral tegmental region to limbic structures**, particularly the **limbic cortex** * generally exerts a **slow inhibitory** action on CNS neurons * best characterized on **dopamine-containing substantia nigra neurons**, where **D2 receptor activation opens potassium channels** via the GCP

DOPAMINE

# **MONOAMINES | DOPAMINE** synthesized from ____

Ldopa

# **MONOAMINES | DOPAMINE** degraded by | major degradator

MAO B

# **MONOAMINES | DOPAMINE** all receptors are ____

metabotropic

# **MONOAMINES | DOPAMINE PATHWAYS** **substantia nigra** to **striatum**

NIGROSTRIATAL PATHWAY

# **MONOAMINES | DOPAMINE PATHWAYS** controls **vomiting**

chemoreceptor trigger zone (CTZ) of the medulla

# **MONOAMINES | DOPAMINE PATHWAYS** regulate **prolactin** release

hypothalamus to intermediate lobe ofpituitary

a monoamine that can **induce vomiting** and can **inhibit** **prolactin release**

DOPAMINE

# **DOPAMINE DISORDERS** result from **overstimulation** of dopamine receptors | too much dopamine in cytosis

PSYCHOSES

# **DOPAMINE DISORDERS** caused by **too little** dopaminergic input from the substantia nigra into the striatum | **low dopamine levels**

PARKINSON'S DISEASE

# **MONOAMINE** * formed from **tryptophan** (hydroxylated then carboxylated) * released from **inhibitory** neurons * stimulates **5HT** receptors * all receptors are **metabotropic**, except **5HT3** (**ionotropic**) * has **inhibitory actions** in most areas of the CNS * has been implicated with the regulation of virtually **all brain functions** * **depression**, **attention deficit disorder**, and **headaches** have been attributed to its imbalance

SEROTONIN, 5HT

# **MONOAMINE | SEROTONIN** formed from ____

tryptophan

# **MONOAMINE | SEROTONIN** released from ____

inhibitory neurons

# **MONOAMINE | SEROTONIN** **ionic** receptor

5HT3

# **MONOAMINE | SEROTONIN** disorders that have been attributed to **serotonergic imbalance**

depression ADHD headahce

# **MONOAMINE** * exclusively made by neurons in the **tuberomammillary nucleus (TMN)** in the posterior hypothalamus * modulate **arousal**, **attention**, **feeding behavior**, and **memory** * H1 - H4 * **metabotropic** * **centrally acting** are generally used for their **sedative properties** * antagonism of **H1** receptors is a **common side effect** of many drugs including some tricyclic **antidepressants** and **antipsychotics**

HISTAMINE

# **MONOAMINE | HISTAMINE** exclusively made by neurons in the ____

tuberomammillary nucleus (TMN)

# **MONOAMINE | HISTAMINE** **antacid** receptor

# **MONOAMINE | HISTAMINE** **antihistamine** receptor

# **MONOAMINE | HISTAMINE** **centrally acting** antihistamines are generally used for their ____ properties

sedative

# **MONOAMINE | HISTAMINE** **antagonism** of ____ receptor is a **common side effect** of many drugs

* generally packaged in **large**, **dense core vesicles** * released neuropeptides may act **locally** or may **diffuse long distances** and **bind to distant receptors** * **metabotropic** and primarily serve **modulatory roles** in the NS * implicated a wide range of **CNS functions**: reproduction, social behaviors, appetite, arousal, pain, reward, learning, & memory

NEUROPEPTIDES

# **NEUROPEPTIDES** * **endorphines**, **enkephalins**, & **dynorphins** * **metabotropic** - mu, kappa, delta * in times of **stress** and **pain**, **endogenous peptides** act to **relieve pain**

OPIOIDS

opioid analgesic

morphine

# **NEUROPEPTIDES** * released from primary sensory neurons in the **spinal cord** and **brainstem** and causes a **slow excitatory** postsynaptic potential * plays an important role in transmitting **pain stimuli**

SUBSTANCE P | P - **pain**

* peptide NTs produced in the **lateral** and **posterior hypothalamus** * also called **hypocretins** * bind to **two GPCR**, OX1 & OX2 * **excitatory** * associated with **wakefulness** * project to and activate monoamine and acetylcholine neurons involved in **sleep-wake cycles** * also involved in **energy homeostasis**, **feeding behaviors**, **autonomic function**, and **reward**

OREXIN

# **OREXIN** are also called as

hypocretins

# **OREXIN** two GPCR that it binds to

OX1 & OX2`

# **OREXIN** associated with

wakefulness

# **OREXIN** involved in

sleep-wake cycles

# **OREXIN** **animals** **lacking orexin** or its receptor have ____ and ____

narcolepsy disrupted sleep-wake patterns

# **OTHER SIGNALLING SUBSTANCES** * endogenous cannabinoids can function as **retrograde** synaptic messengers * released from postsynaptic neurons and **travel backward** across synapses, activating CB1 receptors on presynaptic neurons and suppressing transmitter release * cannabinoids may affect **memory**, **cognition**, and **pain perception**

ENDOCANNABINOIDS

# **OTHER SIGNALLING SUBSTANCES** * generated when **neuronal nitric oxide synthase (NOS)** is **activated** by **calcium-calmodulin** and activation of **NMDA receptors** - increases intracellular calcium * **longterm depression** of synaptic transmission in the cerebellum

NITRIC OXIDE

# **OTHER SIGNALLING SUBSTANCES** * ATP found in and released from catecholinergic synaptic vesicles, and may be converted to adenosine extracellulary by nucleotidases * **adenosine** in the CNS acts on **metabotropic A1 receptors** * **Presynpatic A1** receptors **inhibit calcium channels** and **inhibit release** of both **amino acid** and **monoamine transmitters** * involved in **memory**, **wakefulness**, and **appetite**, and may play roles in **multiple neuropsychiatric disorders**

PURINES

# **OTHER SIGNALLING SUBSTANCES | PURINES** **nonselective ligand-gated** cation channels

P2X

# **OTHER SIGNALLING SUBSTANCES | PURINES** metabotropic

P2Y