Monoamines
Acetylcholine
Amino Acids
Neurotransmitters
Soluble Gases
Peptides
Lipids
Nucleosides
Figure 4.9 Acetylcholinergic Pathways in a Rat Brain
REM sleep
(basal
forebrain)
learning
memory
+
Monoamines

The Monoamines

A class of amines that includes indolamine, such as serotonin; and
catecholamines, such as dopamine, norepinephrine, and
epinephrine.

See Table 4.1
Catecholamines
Indolamines
Dopamine
Serotonin
Norepinephrine
Epinephrine
Figure 4.13 Dopaminergic Pathways in a Rat Brain
Nigrostrial = cell bodies in substantia nigra send axons to striatum = movement (parkinson’s)
Mesolimbic = VTA to limbic system including NA, AMYG, & HIP (NA important for rewarding
effects of stimuli including drugs of abuse)
Mesocortical = VTA to prefrontal cortex (short-term memories, planning and problem solving)
Figure 4.16 Noradrenergic Pathways in a Rat Brain
Increased vigilance, attentiveness to events in the environment
+
NE

Adrenergic receptors (all sensitive to NE and E)

β1- and β2-adrenergic receptors

α1- and α2-adrenergic receptors

All are metabotropic, coupled to G proteins that control
production of second messengers

All are found in various organs in addition to the brain

Adrenergic receptors produce both excitatory and inhibitory
effects but, in general, the behavioral effects of NE release are
excitatory
Figure 4.18 Serotonergic Pathways in a Rat Brain
Behavioral effects are complex
Regulation of mood
Control of eating, sleep and
arousal
Regulation of pain
Dreaming
+
5-HT

Like NE, 5-HT is released from varicosities rather than terminal
buttons

There are least 9 different types of 5-HT receptors

5-HT1A-1B, 5-HT1D-1F, 5-HT2A-2C and 5-HT3

all are metabotropic except the 5-HT3 receptor, which is
ionotropic

5-HT3 receptor controls a chloride channel, which means it
produces IPSPs

Drugs that inhibit the reuptake of 5-HT (SSRIs) treat mental illness


Fluoxetine – treats depression, anxiety, and OCD
Fenfluramine – treats obesity
+
GABA
Glutamate
Amino Acids
Glysine
+Figure 4.19 NMDA Receptor
decreased
Increased
Indirect
antagonist
4 binding sites on exterior and 2
binding sites deep in ion channel
•when channel is open both Na and
Ca ions move inside the cell, causes
depolarization
•Ca also serves as 2nd messenger
and activates enzymes important for
learning and memory
•Must also have glycine binding for
channel to open
•Also Mg ion must not be attached to
Mg binding site
•Mg repelled if membrane is partially
depolarized
•need glutamate & depolarization
•voltage and NTS-dependent ion
channel
+ Figure 4.20 GABA
A
Receptor
•Barbiturates, steroids and
benzodiazepines all promote
activity of GABA receptor (indirect
agonists)
•Picrotoxin inhibits activity of
GABA receptor (indirect
antagonist)
+  Peptides
Endogenous Opioids



Enkephalin – one of the endogenous opioids.

Opiate receptors


A class of peptides secreted by the brain that act like opiates
(opium, morphine, heroin).
At least 3 different types: μ(mu), δ(delta) and κ(kappa)
Endocannabinoids

Binds with THC, the active ingredient of marijuana.

Anandamide – the first cannabinoid to be discovered.

2-arachidonyl glycerol (2-AG)
 Nucleosides

Adenosine – a nucleoside; a combination of ribose and
adenine; serves as a neuromodulator in the brain.

Adenosine receptors are coupled to G proteins and open
potassium channels (IPSP)

Caffeine – a drug that blocks adenosine receptors.
+
Soluble Gases
 Soluble

Gases
NO and CO
 Nitric
Oxide (NO) – a gas produced by cells in the
nervous system; used as a means of
communication between cells.


Released by diffusion as soon as it is produced
Triggers production of second messengers (cyclic GMP) in
adjacent cells
 Functions:




Control of muscles in the wall of the intestines
Dilates blood vessels in brain
Stimulates the changes in blood vessels that produce
penile erections
May play a role in learning
+
Mind and
Brain
Methods and Strategies of
Research
Chapter 5
+
Chapter Overview

Experimental Ablation

Recording and Stimulating Neural Activity

Neurochemical Methods

Genetic Methods
+
Evaluating the Behavioral Effects
of Brain Damage
Experimental Ablation

Lesion: any type of wound or injury (generic)

Ablation: A type of lesion in which a brain
region is removed or destroyed.


presumably, the functions that can no longer be
performed are the ones the region previously
controlled (a.k.a. – lesion study).
(never this easy)
Brain Lesion Studies
 Producing Brain Lesions
1. Aspiration – suck it out

Only useful for surface; not common
2. Electrolytic Lesion- current
through lesions
3. Radio Frequency Lesion
(30kHz and above)

An alternating current of a very
high frequency capable of
destroying neural tissue.
Electrolytic lesion of LC
(lower) and sham
operated
controls(upper)
+
Experimental Ablation
4. Knife cuts
may damage surrounding area
 Used to eliminate conduction in a nerve or tract

5. Cryogenic blockade

“reversible lesion”
Copyright © 2006 by Allyn and Bacon
Neurons near the tip are
cooled until they stop firing
Copyright © 2006 by Allyn and Bacon
Brain Lesion Studies
7. Excitotoxic Lesion

A brain lesion produced by
intracerebral injection of
an excitatory amino acid,
such as kainic acid.
 Kainic or ibotenic acid – destroy
cell bodies
8. Selective lesion: target a
specific cell type

Neural poisons (neurotoxins)
selectively target specific nervous
system components
 6-hydroxydopamine (6-OHDA)
– destroys noradrenergic and
dopaminergic neurons
Sham
Selective NE
lesion
Sham Lesion

All the steps of producing a brain lesion except
the one that actually causes the brain damage.
+
Experimental Ablation
9. Reversible brain lesions
 Effectively
anesthetize the brain region
 Inject local anesthetic into brain (muscimol;
lidocaine)
 Reversible in that the effects wear off
 Caution: damage of injection
+
Stereotaxic Surgery
 Stereotaxic

Surgery
Brain surgery using a stereotaxic apparatus to position an
electrode or cannula in a specified position of the brain.
Requires a stereotaxic atlas to identify the location of the
brain area(s) of interest.
+
Stereotaxic Surgery

The Stereotaxic Atlas
 A collection of drawings of sections of the brain of a
particular animal with measurements that provide
coordinates for stereotaxic surgery.
 Correspond to frontal sections taken at various
distances rostral and caudal to bregma
 Each page of the atlas is labeled according to the
distance of the section anterior or posterior to bregma
+ Figure 5.3 Rat Brain and Skull
Figure 5.4 Stereotaxic Atlas
+
Stereotaxic Atlas
+
Anterior-Posterior
Dorsal
Ventral
Medial-Lateral
+
Sample sections from Atlas
+
Stereotaxic Surgery

The Stereotaxic Apparatus
 A device that permits a surgeon to position an electrode
or cannula into a specific part of the brain.
 Includes a head holder, a holder for an electrode (or
cannula), calibrated mechanism that moves the electrode
holder in measured distances along the 3 axes: anteriorposterior, dorsal-ventral, lateral-medial
+ Figure 5.5 Stereotaxic Apparatus
Copyright © 2006 by Allyn and Bacon
+
Stereotaxic Surgery in Humans
+
Experimental Ablation
 To
verify the precise location of
the brain damage (or cannula
placement, etc)
 Histological

Methods
Fixation and Sectioning

Fixative – chemical such as
formalin; used to prepare and
preserve body tissue.
 Formalin – aqueous solution of
formaldehyde gas
 Stops autolysis, hardens the
very soft and fragile brain,
and kills any microorganisms
that might destroy it
+
Experimental Ablation


Perfusion – process by which an animal’s blood is replaced
by a fluid such as a saline solution or a fixative in preparing
the brain for histological examination.
Microtome – instrument that produces very thin slices of
body tissues
+
Experimental Ablation
 Staining
techniques are typically methods
which are used to visualize specific
anatomy
 Structural
 Cellular
 Common: Nissl
 Dye: cresyl
stain
violet
 Stains: Nissl bodies
(mostly nuclear)