Neurotransmitters

Acetylcholine

Monoamines

Amino Acids

Peptides

LipidsNucleosides

Soluble Gases

Figure 4.9 Acetylcholinergic Pathways in a Rat Brain

(basal forebrain)

REM sleep

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 complexRegulation of moodControl of eating, sleep and arousalRegulation of painDreaming

+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

+

Amino Acids

Glutamate

GABA

Glysine

+Figure 4.19 NMDA Receptor

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

decreased

Increased

Indirect antagonist

+Figure 4.20 GABAA Receptor

•Barbiturates, steroids and benzodiazepines all promote activity of GABA receptor (indirect agonists)•Picrotoxin inhibits activity of GABA receptor (indirect antagonist)

+ Peptides Endogenous Opioids

A class of peptides secreted by the brain that act like opiates (opium, morphine, heroin).

Enkephalin – one of the endogenous opioids. Opiate receptors

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

+

Methods and Strategies of ResearchChapter 5

Mind and Brain

+Chapter Overview

Experimental Ablation

Recording and Stimulating Neural Activity

Neurochemical Methods

Genetic Methods

+

Evaluating the Behavioral Effects of Brain Damage

Experimental AblationExperimental Ablation

LesionLesion: any type of wound or injury (generic)

AblationAblation: 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 StudiesBrain Lesion Studies

Producing Brain Lesions1. 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)

Electrolytic lesion of LC (lower) and sham operated controls(upper)

+Experimental Ablation4. 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

Copyright © 2006 by Allyn and Bacon

Neurons near the tip are cooled until they stop firing

Brain Lesion StudiesBrain Lesion Studies7. 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

ShamShamSelective NE lesionSelective 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 SkullFigure 5.4 Stereotaxic Atlas

+Stereotaxic Atlas

+ Anterior-Posterior

Medial-Lateral

DorsalVentral

+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: anterior-posterior, 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 stain Dye: cresyl violet Stains: Nissl bodies

(mostly nuclear)