Brain AnatomyNeurotransmission

& Brain Neurotransmitters

Brain Structures

Cerebral Hemisphere - 1/2 of Cerebrum

Cerebral

Cortex

(Grey Matter)

Cerebral Cortex

The cerebrum’s surface—the cerebral cortex—is convoluted into hundreds of folds.

The cerebral cortex is where all the higher brain functions take place.

Cerebral Lobes Parietal Lobe

•Touch•Smell•Taste•Sensory and spatial awareness

Temporal Lobe

•Emotions•Smelling•Tasting

Frontal Lobe

Higher cognitive functions.•Problem solving•Memory

Occipital Lobe

VisionRecognition

Limbic Lobe

Limbic Lobe

The limbic lobe is located deep in the brain, and makes up the limbic system.

Cingulate cortex/

Limbic cortex

Corpus callosumThe limbic system is the area of the brain that regulates emotion and memory. It directly connects the lower and higher brain functions

The Basal Ganglia & StriatumBasal Ganglia/Striatum:

Caudate nucleus

Putament

Deep below the cerebral cortex there are interconnected areas of grey matter collectively known as the "basal ganglia" (basement structures).

Shown above (in green) is the largest structure in the basal ganglia called the striatum

Play an important role in motivation, planning and coordinating motor movements and posture.

Brain Structures

Brain Stem

= (Midbrain+Hindbrain) - Cerebellum

Thalamus

Thalamus means “inner room” in Greek, as it sits deep in the brain at the top of the brainstem.

The thalamus is called the gateway to the cerebral cortex, as nearly all sensory inputs pass through it to the higher levels of the brain.

Hypothalamus

The hypothalamus sits under the thalamus at the top of the brainstem. Although the hypothalamus is small, it controls many critical bodily functions and set points:

• Controls autonomic nervous system

• Center for emotional response and behavior

• Regulates body temperature

• Regulates water balance and thirst

• Controls sleep-wake cycles

• Controls endocrine system

The hypothalamus is shaded blue. The pituitary gland extends from the hypothalamus.

Brain Structures

Brain Stem

= (Midbrain+Hindbrain) - Cerebellum

The Brainstem

Most primitive part of the brain

―controls the basic functions of life: breathing, heart rate, swallowing, reflexes to sight or sound, sweating, blood pressure, sleep, and balance.

Midbrain

Pons

Medullaoblongata

Cerebellum

The cerebellum is connected to the brainstem, and is the center for coordination of body movement and balance.

The Ventricles

The ventricles are a complex series of spaces and tunnels through the center of the brain.

The ventricles secrete cerebrospinal fluid (CSF), which suspends the brain in the skull.

The ventricles also provide a route for chemical messengers that are widely distributed through the central nervous system.

Cerebrospinal Fluid

Cerebrospinal fluid is a colorless liquid that bathes the brain and spine.

It is formed within the ventricles of the brain, and it circulates throughout the central nervous system.

Cerebrospinal fluid fills the ventricles and meninges, allowing the brain to “float” within the skull.

Blood-Brain Barrier

The blood brain barrier consists of cells tightly packed around the capillaries of the CNS

Blood-Brain Barrier

Drugs that cross the BBB and enter the brain must be non-

protein bound, non-ionized, and highly lipid soluble

Part II:Neurotransmission

Brain Cells

• Nerve Cells or Neuron

• Variety of Supporting Cells– In CNS (brain and spinal cord) supporting

cells consist mostly of neuroglial cells.

neuron

Neurons & Neuron StructureNeurons are the basic building blocks of the nervous system.

These specialized cells are the information-processing units of the brain responsible for receiving and transmitting information.

Signaling along Brain Circuits

Signaling along brain circuits involves 2 steps

1. Nerve Impulse Conduction: • passage of an electrical signal (a positive

deflection of the membrane voltage) along a neuron.

2. Neurotransmission or Synaptic Transmission: • The transmission of a nerve impulse from one

neuron to another via a chemical signal.

Neurotransmission (also called Synaptic Transmission)

How nerve cells communicate with each other

Synaptic/Neurotransmission

The process is quite complex but it is important to understand it because the synapse is a target for many common drugs

The Synapse– Nervous impulses are transmitted from one neuron to

another across structures called synapses.– Synapses separate neurons by a small gap called the

synaptic cleft– Neurons communicate across the synaptic cleft using

neurotransmitters.

Pre-synaptic terminalPost-synaptic

terminal

Neurotransmission

Steps in Neurotransmission

1. The nervous impulse (a +ve deflection of the voltage of the neuron) or action potential travels down the axon and arrives at the axon terminal.

2. The +ve deflection of the voltage of the axon terminal opens voltage-activated Calcium channels (pores in the membrane that are specifically permeable to Calcium ions) and Calcium ions enter the axon terminal.

3. Neurotransmitter molecules are present in the terminal of the neurons in little packages called synaptic vesicles.

4. In response to Calcium entry these synaptic vesicles fuse to the neuronal membrane and the neurotransmitters are released into the synaptic cleft.

5. Neurotransmitters bind to receptors on the post-synaptic membrane.

6. The activated post-synaptic receptors either stimulate (excite or depolarize, i.e make more +ve) or inhibit (hyperpolarize, i.e make more –ve) the postsynaptic neuron.

Steps in Neurotransmission (contd)

Termination of Neurotransmission

1. Neurotransmitter can diffuse away from the synapse.

2. Neurotransmitters may be broken down by enzymes present in the synapse.

3. Neurotransmitters may be pumped back into the presynaptic terminal ().

― Once back in the presynaptic terminal they may be repackaged into synaptic vesicles.

― Or they may be broken down by enzymes present in the presynaptic terminal (e.g. as in the case of monoamine neurotransmitters by the enzyme monoamine oxidase (MAO)).

1. Nerve Conduction

How does a neuron or nerve fiber generate and conduct an electrical signal?

Resting Membrane Potentials & Basis for Neuronal Electric Currents

The inside of a neuron is negatively charged with respect to the outside

-60 mv

Intra- & Extra-Cellular Ionic Concentrations

K+ (140 mM)

Na+ (4 mM)

Cl- (4 mM)

Ca++ (0.1 nM)

K+ (4 mM)

Na+ (140 mM)

Cl- (140 mM)

Ca++ (2 mM)

Intracellular Extracellular

The Sodium (Na+)-Potassium (K+) Pump is responsible for maintaining High K+ and Low Na+ concentrations inside the neuron or cell.

It is the target of many drugs.

Concentration of Ions Inside a Neuron

Concentration of Ions Outside a Neuron

K+ Channels are Open at Rest• The reason cells or neurons are

negatively charged is that K+ (Potassium) channels are normally open at rest.

• K+ will flow out of the neuron through these K+ specific pores (K+ channels) , taking away +ve charge and leaving the neuron with a net negative charge.

Ion Channels & Cellular Excitability

• If a neuron or cell becomes more negatively charged it is said to be hyperpolarized and is less excitable or less likely to conduct a nerve impulse or action potential.

• If a neuron or cell becomes more positively charged it is said to be depolarized and is more excitable or more likely to conduct a nerve impulse or action potential.

K+ (140 mM)

Na+ (4 mM)

Cl- (4 mM)

Ca++ (0.1 nM)

K+ (4 mM)

Na+ (140 mM)

Cl- (140 mM)

Ca++ (2 mM)

-60 mV

Ion Channels & Cellular Excitability

• Drugs that activate K+ channels make a neuron less excitable.

• Drugs that activate Na+ channels ↑ excitability

• Drugs that activate Cl- channels ↓ excitable

• Drugs that activate Ca++ channels ↑ excitable

K+ (140 mM)

Na+ (4 mM)

Cl- (4 mM)

Ca++ (0.1 nM)

K+ (4 mM)

Na+ (140 mM)

Cl- (140 mM)

Ca++ (2 mM)

-60 mV

Ion Channels & Cellular Excitability

• K+ channels open→ hyperpolarization (↑ -ve), ↓ excitable

• Na+ channels open→ depolarizaton (↑ +ve), ↑ excitable

• Cl- channels open→ hyperpolarization (↑ -ve), ↓ excitable

• Ca++ channels open→ depolarization (↑ +ve), ↑ excitable

K+ (140 mM)

Na+ (4 mM)

Cl- (4 mM)

Ca++ (0.1 nM)

K+ (4 mM)

Na+ (140 mM)

Cl- (140 mM)

Ca++ (2 mM)

-60 mV

Action Potential• An action potential (or nerve impulse) is a transient alteration of the

transmembrane voltage (or membrane potential) across an excitable membrane generated by the activity of voltage-gated ion channels embedded in the membrane (from Neuroscience. 4th ed.. Sinauer Associates).

• Action potentials are pulse-like waves of +ve voltage that travel along axons of neurons and muscle cell including cardiac muscle.

Myelin and Propagation of Action Potentials

• Many axons in the CNS are surrounded by oligodenrocytes that wrap around the axon forming a sheath of myelin.

• Myelin provides electrical insulation that aids the propagation speed of the Action Potential.

Nodes of Ranvier

Myelinated Axons

Multiple SclerosisMultiple sclerosis (MS), is an autoimmune disease of in

which the body's immune response attacks a person's brain and spinal cord (CNS), leading to demyelination.

Immune cells attacking myelin

How Neurotransmitters Generate Axon Potentials

• Neurotransmitters either directly (by binding to ionotropic receptors) or indirectly (by binding to metabotropic receptors) activate ion channels expressed on the postsynaptic neuron.

• These ion channels can either depolarize (excite or make more +ve) or hyperpolarize (inhibit or make more negative) the postsynaptic membrane.

• If the sum of all the actions of the neurotransmitters acting at the postsynaptic membrane depolarizes (excites) the postsynaptic neuron sufficiently then the action potential chain reaction is initiated at the neuron.

Neurotransmitter Receptors

Metabotropic Receptors

Bind to neurotransmitters & modulate ion channels indirectly

Ionotropic Receptors

Are ion channels that open upon binding to neurotransmitter

Neurotransmitter molecule

Neurotransmitter Receptors are the targets of many drugs

Glutamate & GABA Neurotransmitters

Glutamate

– Primary excitatory neurotransmitter in the brain.

– Major receptor is a non-specific cation channel

GABA

– Primary inhibitory neurotransmitter in the brain.

– A major receptor is a Cl- ion channel.