Hormones and Activity, Sensory Perception and Sensorimotor Function

WHAT IS ACTIVITY?

Defined in different ways:

"general activity" "open field activity" "locomotor activity" "running wheel activity" "social play"

WHAT IS SENSORY FUNCTION?

taste olfaction vision pain analgesia

WHAT IS SENSORIMOTOR FUNCTION?

-> Complex behaviors involving integration of motor function with sensory perception.

SEX DIFFERENCES IN ACTIVITY

open field activity - this locomotor activity in a large open area

what is measured: distance travelled, number of quadrants entered, etc.

In rats - intact female rats travel a greater distance in an open field than do male rats.

intact female > OVX female

intact male = CAST male

but -> OVX > CAST

--> Thus, estrogen activates open field activity, but there is ALSO an underlying sex-related difference due to an organizational effect of hormones on the brain.

In mice - 2M females < 0M females in open field activity, supporting the idea of an organizational effect of perimatal hormones.

What is the role of sexual differentiation in sexual dimorphisms in open field activity?

It seems that estrogen during a second (later) period of postnatal development is necessary to feminize open field behavior.

(What does THAT mean?)

"critical period #1" "critical period # 2"

|--------------| |--------------------------| |-----------------------------------------------

gestation pre-pubertal period post-pubertal/adult period

Testosterone (converted to estrogen) during period #1 masculinizes the brain for sexual behavior and suppresses open field activity (masculinizes).

Estrogen (in female) during period #2 feminizes the brain for open field activity.

Thus:

Testosterone during period #1 = male

No Testosterone during period #1 and Estrogen during period #2 = female

no E or T = in between male and female

RUNNING WHEEL ACTIVITY

In females there is estrous cycle dependent variation in running wheel activity, with estrus > other days of the cycle.

This effect of estrous cycle appears to be dependent on the the effects of estrogen on the brain. Earlier work by Zucker and Wade suggested that estrogen was acting in the POA, because estrogen implants into the POA increased activity in a running wheel (when given to OVX rats). However, more recent work by Ed Roy at the university of Illinois has suggested that estrogen in the striatum has the same effect - and points out that cannulae implanted into the POA (that produced an effect on running wheel behavior) pass through the striatum, potentially delivering estrogen to the striatum as well as POA. Thus the site of estrogen action in the brain to affect running wheel activity is controversial. (I would bet on the striatum as the primary site of estrogen's effect on running wheel behavior).

Social Play (Active Play Behavior)

Males more active than females. As discussed previously, this is apparently due to the organizational effects of testosterone or DHT during the perinatal period.

Furthermore, corticosterone during the perinatal period inhibits the masculinization of social play.

-> neither testosterone or corticosterone have activational effects on this behavior

Testosterone is thought ot act in the amygdala to induce these effects, the amygdala also has glucocorticoid receptors, so the coticosteroids may also act there.

SENSORY SYSTEMS

1) Chemical sensation

a) pheromones detected by the vomeronasal organ

-> in rats there is a hormone dependent preference for conspecifics

-> in male hamsters there is an absolute requirement for vomeronasal stimulation for the induction of male sexual behavior.

In Mice there are other pheromone-dependent events -

Lee-Boot effect - male induced depression of estrus in females

Whitten effect - male induction of estrus in females

Bruce effect - male blockade of pregnancy

van den Berg effect - male accelerates puberty in females

b) taste

-> females have stronger preferences for sweetness or saltiness than do males

2) Visual acuity - females have greater acuity than do males - this is estrogen dependent. Women show a greater acuity during the periovulatory phase of the cycle than at other times during the menstrual cycle.

3) Pain sensitivity and analgesia

female > males sensitivity to foot shock ot tactile stimulation

male> female analgesia induced by stress or morphine

SENSORIMOTOR INTEGRATION

Let's put these two types of sex differences and hormonal influences together and look at the neural systems mediating sensorimotor integration.

From clinical studies we know that the neural systems mediating sensorimotor function are affected by gonadal hormones. Example 1 - There is a sex differnece in the age of onset of Parkinson's Disease. Women tend to exhibit symptoms later than men and are usually post-menopause. Example 2 - Women on birth control pills with high doses of estrogen or during pregnancy have been reported to exhibit symptoms called chorea - abnormal movements usually associated with basal ganglia function.

What are the neural systems that might be involved in these functions?

-> pathway for sensory information to get into the brain via the ascending pathways in the spinal cord

-> integration occurs at the level of the cortex (pyramidal system); the basal ganglia and cerebellum (extrapyramidal systems).

Basal Ganglia (I drew a schematic drawing of the relations among the subregions of the basal ganglia and connections to cortex as well as thalamus - there is a fancy diagram of the same thing in your text).

caudate + putamen = striatum

globus pallidus

substantia nigra

The connections go like this:

1) the main processing is thought to be in the striatum, where lesions disrupt species-specifc motor programs, cause abnormal motor behaviors to occur spontaneouly, and result in sensory neglect (depending on where the lesions are and which particular cells are damaged - more later).

2) The dopamine cell bodies are in the substantia nigra (found in the midbrain), these cells send their axons to the striatum. These are the cells that die in Parkinson's Disease.

3) There is input to the striatum from all areas of cortex - motor cortex, sensory cortex, frontal cortex, visual cortex, etc. The striatum is monitoring EVERYTHING that goues on. It also receives input from thalamus (where most information is relayed) so it knows what processing is also occurring.

4) The major output is from the striatum to the globus pallidus, which then projects to the thalamus.

-> The basal ganglia integrate information to execute complex simultaneous and sequential or species specific motor programmes.

So, what happens when the basal ganglia is damaged?

Example 1) Parkinsons's Disease (Dopamine cells in substantia nigra that send axons to striatum die).

symptoms are seen after 60-80% of the dopamine neurons have died, they include - bradykinesia (slowness of movement), resting tremor, sensory neglect, aphasia and adipsia (don't eat and don't drink unless highly palatable), loss of affect.

Example 2) Huntington's disease - loss of neurons in the striatum (due to genetic defect)

symptoms: cognitive deficits, chorea (dance-like movements, uncontrollable), ballism (rapid flick-like movements of limbs and facial muscles).

Drugs that act on the dopamine neurons in the basal ganglia (where 90% of the dopamine in the brain is found) can be used to behaviorally assess the effects of hormones on this neural system. Amphetamine induces dopamine release from dopamine terminals. When administered to rats they become hyperactive, exhibit locomotor activity and stereotyped behaviors (repetetive movements of the forearms and face/mouth/head & neck). Studies (from my lab and others) have shown that the behavioral response to amphetamine varies with the estrus cycle - it is greater when estrogen is high on estrus. Furthermore, ovariectomy decreases the behavioral response to amphetamine, and estrogen restore the response to amphetamine to that seen in the intact rat. There are also sex differneces in the behavioral response to amphetamine - female rats exhibit a greater behavioral response than do males (intact or castrated).

How does estrogen affect dopamine neurons in the striatum? ->Estrogen increases striatal dopamine release and striatal dopamie turnover.

So, does this effect of estrogen on the response to amphetamine have any importance for normal behaviors that the rat, or is it just a drug effect?

In one experiment from my lab, we looked at the effect of estrous cycle on performance of female rats trained to walk across a suspended beam. The feet of the rats were painted with tempura paint, and their footprints were scored for placement on top of the beam (correct placement) or hanging off the side (a footfault). We found that female rats in estrus made fewer footfaults than on other days of the cycle.

This result told us tha sensory motor function varied with the estrous cycle, but did not tell us where hormones were acting to produce this effect. So in the next experiment we took ovariectomized female rats and deliver estradiol into the striatum. We found that within 4 hour after treatment, there was a significant improvement in performance, indicating that estrogen could affect sensorimotor function by acting directly on the striatum.