coordinates could be used. Extracellular unit recordings were made by using
micropipettes filled with a 4:1 mixture of NaCL and KCl; the tip was broken
back to give electrode resistances of the order of 1 megohm. Higher
impedance (10-megohm) electrodes were often necessary for single unit
isolation in the small-celled posterior area of n. rotundus. Amplifying and
display procedures were conventional, using Neurolog modules, and the inte-
grated spontaneous rates were written out on a Grass Polygraph. In the
usual experiment, the micropipette was inserted into the thalamus of the
pigeon until an appropriately responding, spontaneously active single unit
was isolated. Three types of neurones were used: (i) nonvisual units from
the dorsal thalamus overlying nucleus rotundus; (ii) nonselective units
from posterior rotundus (2) (these units responded to any stimulus configura-
tion that moved); and (iii) directionally selective, anterior rotundal
neurones which also preferred small target sizes (5° arc). During the
recording period the animal was undisturbed, in an isolation chamber with
its right eye closed and its left eye viewing a screen whose luminance was
2.0 footcandles. Qualitative response categorization was achieved by

aural evaluation of unit responses to manually moved dark cardboard targets
positioned against the tangent screen. Dilute ethanol was administered
intravenously, or intramuscularly, after a 45-min control recording. Doses
are given as milliliters of 95 percent ethanol per kilogram of body weight.
Only those units were used which could be followed for at least 1 hour post-
treatment and which gave no signs of damage discharge or sudden spike
configuration changes during the recording period.

III. Results. ;
We recorded from a total of 36 neurones.

Twenty anterior rotundal neurones were studied. Ethanol always
produced an inhibition of spontaneous activity in these units. Threshold
dose was 0.05 ml/kg. Doses of 0.20 ml/kg or higher completely blocked
spontaneous activity, though activity evoked by moving stimuli was not
completely blocked. Indeed, periodic testing with moving stimuli was the
only way of determining that the unit had not been killed by the ethanol or
otherwise "lost." Doses around 0.10 ml/kg induced a 50-, to 80-percent drop
in spontaneous rate, with a pild depression of the evoked activity examined
(Fig. 1}. Duration of action of ethanol at 0.10 ml/kg was 60 to 120
minutes. Duration of effect of higher doses of ethanol could not be
determined, since the units usually could not be "held" (recorded from) for
more than 3 hours post-ethanol, and recovery from inhibition did not occur
within this time. . .

Ethanol effects on the 10 posterior rotundal units studied were
complex. A dose of 0.10 ml/kg produced, in the six units tested, a 30- to
50-pa@cent inhibition of spontaneous rate beginning 2 to 5 minutes after
injection and lasgjng for 2 to 10 minutes. This was followed by an increase
in rate to 1.5 to 3.0 times mean control levels. The’ increase lasted 60 to
120 minutes (Fig. 1). Again, the duration of effect was difficult to assess,

2

4
t


1.

5.

10.

ll.

} »

References

Adams, A. J., B. Brown, M. C, Flom, R. T, Jones, and A. Jampodsky:
Alcohol and Marijuana Effects on Static Visual Acuity, AMER. J.
OPTOM., 52:729-735, 1975.

Benowitz, L. I., and H. J. Karten: Organization of the Tectofugal
Visual Pathway in the Pigeon, J. COMP. NEUROL., 167:503-520, 1976,

Bernhard, C. G., B. Knave, and H. E. Persson: Differential Effects
of Ethyl Alcohol on Retinal Functions, ACTA PHYSIOL. SCAND., 88:373-
381, 1973.

Brown, B., A. J. Adams, G. Haegerstrom-Portnoy, R. T. Jones, and

M. C. Flom: Effects of Alcohol and Marijuana on Dynamic Visual
Acuity I. Threshold Measurements, PERCEPT. PSYCHOPHYS., 18:441-446,
1975.

Christensen, C. A., and L. G. Underleider: Pulvinar Lesions in
Monkeys Produce Abnormal Scanning of Complex Visual Arrays,
NEUROSCIENCE ABSTRACTS, 3:556, 1977.

Dow, B. M.: Central Mechanisms of Vision: Parallel Processing,
FED. PROC., 35:54-59, 1976.

Flom, M. ,C., B. Brown, A. J. Adams, and R. T. Jones: Alcohol and
Marijuana Effects on Ocular Tracking, AM. J. OPTOM. PHYSIOL. OPT.,
53:764-773, 1976.

Godfraind, J. M., M. Meulders, and C. Veraart: Visual Properties
of Neurons in Pulvinar, Lateralis Posterior and Nucleus Suprageniculatus
Thalami in the Cat, BRAIN RES., 44:503~-526, 1972.

Guedry, F. E., Jr., R. D. Gilson, D. J. Schroeder, and W. E. Collins:
Some Effects of Alcohol on Various Aspects of Oculomotor Control,
AVIAT. SPACE ENVIRON. MED., 46(8):1008-1013,, 1975.

r
Hansteen, R. W., R. D. Miller, L. Lonero, L. D. Reid, and B. Jones;
Effects of Cannabis and Alcohol on Automobile Driving and Psychomotor
Tracking, ANN. N.Y. ACAD. SCI., 282:240-256, 1976.

Holmes, P. W.: Ethanol Consumption by.Pigeons under Stress, Q. J. STUD.
ALCOHOL, 34:764-768, 1973.

Kalant, H.: Ethanol and the Nervous System. Experimental Neuro-
physiological Aspects, INT. J. NEUROL., 9:111-124, 1974.

¥
Karten, H. J., and W. Hodos: A Stereotaxic Atlas of the Brain of
the Pigeon (Columba livia). Johns Hopkins Press, Baltimore, 1967.

7



animals were trained on a task involving orientation to a novel stimulus and
then lesions were made in the pulvinar which, as mentioned above, is, in
part, a functional homolog of n. rotundus. The lesioned monkeys showed
marked abnormalities of visual fixation including an abnormal prolongation
of visual fixations on any one aspect of the stimulus array. This lesion-
induced visual dysfunction is strikingly similar to some of those following
administration of ethanol to human volunteers in doses equal to or greater
than 0.20 ml/kg (19). Thus, at least some of the visual impairment produced
by ethanol may be attributed to its effects on information transfer in the
colliculo-cortical visual projection system. Since the_collicular system
mediates an impressive array of visual functions (27) ,/ ethanol may be
expected to have a variety of subtle and complex effe €s on visual functjons
(7,9,10,17,18, 25,28,30,31) that may be a function of dose and individee!)
(see below).

These effects of ethanol seem to be a result of selective action on
visual neurones since the threshold doses for inhibition of nonvisual dorsal
thalamic cells were substantially higher than the doses required for full
inhibition of the rotundal neurones. | The duration of action of ethanol was
quite long, 60 to 120 minutes at 0.10 ml/kg, and this duration_of action is
roughly in agreement with durations seen in behavioral studtee, Studies of
ethanol effects on other neuronal systems (12,14,15,16,29) repurt relatively
brief, or transient, durations of action, even at quite high doses. (The low
threshold dose and long duration of action of ethanol seen in this study
suggest that the retino-colliculo-cortical visual projection system is a
primary locus (16) for ethanol actionf Thus, in this instance at least, the
effects of ethanol do not seem to bé dué& to a generalized inhibition of .
brain function (7,10,17), but result from actions on specific, functionally
defined target cells a4)15,19)] Under the conditions of our experiment the
spontaneous discharge rate tundal cells is largely determined by mean
retinal illumination (21) (Counce ethanol can affect both retinal (3,33) and
collicular (9) functions, It is not now possible to further define the locus
of ethanol action in this system. }) Ethanol actions on brainstem activating
systems could also be involved . Such activity is not likely to be a
major factor, however, since electrical stimulation of these systems doesn't
have an appreciable effect on mean rate of rotundal firing (21), nor does
wide variation in depth of anesthesia.

The effects of low doses of alcohol, from the 0.05-ml/kg threshold
through 0.15 ml/kg were more complex than the purely inhibitory sequelae of
doses greater than 0.15 ml/kg. Cells in anterior rotundus preferentially
respond to such abstract characteristics of moving ‘stimuli as size, direction
of movement, velocity, figure-ground contrast, etc. (22). These neurones
are inhibited by ethanol at all doses. Spontaneous rate is more sensitive
to the drug than is evoked activity in the sense that an ethanol dose of,
say, 9.10 ml/kg may almost completely block spontaneous firing of a cell
while its responsé’to a moving target does not change qualitatively and is
only moderately inhibited quantitatively (23).( This suggests that ethanol

4



a.

’

since the posterior rotundal units could not be "held" for as long a time as
the anterior cells. Activity evoked by moving stimuli was also enhanced
during the period of increased spontaneous activity. In three and four
additional units, respectively, doses of 0.05 ml/kg and 0.10 ml/kg produced
increases in spontaneous rate of 40 percent and 60 percent. However, these
units could only be "held" for 20 to 30 minutes post-ethanol. In four units,
a dose of 0.20 ml/kg induced an 80-percent reduction in spontaneous activity,
and similarly depressed evoked responses over the 80- to 120-minute periods
that post-drug recording could be taken.

e--6 Posterior Rotundal Untt
180 o— Anterior Rotundal Unit
160 278 tenn en ne,

tert een -.
(40 ‘e.,

% of Control Rate

5 10 15 20 25 30 35 40 48 50 55 60 65 70 75 BO 85 90
Minutes After Ethanol 0.050 mi/kg

Figure 1. +

Ethanol effects were also determined in six nonvisual units in the
thalamus dorsal to posterior rotundus. Inhibition of spontaneous activity
was seen in all, but the dose required was high; 50 percent inhibition
required doses of 0.40 ml/kg or more.

Increasing levels of urethane anesthesia, to 2.3-2.5 gm/kg, had no
observable effects in five each anterior and posterior rotundal neurones
studied in an earlier series of control experiments, though the probability
of finding spontaneously active neurones does inerease with increasing depth
of anesthesia (at least up to 2.4 gm/kg).

iv4\ Discussion.

Ethanol doses equal to or greater than 0.20 ml/kg virtually cut off
spontaneous neuronal activity’ and inhibit visually evoked unit responses in
the nucleus rotundus. Thus, these doses of ethanol severely inhibit the
functions of colliculo-telencephalic visual projection system, just as
would an anatomical lesion of n. rotundus. In fact, the behavioral conse-
quences of such a lesion have recently been studied in monkeys (5). The

v



by doses of ethanol sufficient to induce complete inhibition of anterior
rotundal neurones though, at high doses, the thalamic effects could appear
to be the dominant determinant of behavior changes.

Ethanol ingestion has been implicated as a factor in many aircraft and
‘automobile accidents. One response to this has been attempts to delineate
"safe" levels of blood alcohol~-levels which presumably will not increase the
probability of having an accident. Now, in the present study, 0.20 ml/kg
of ethanol will effectively cut off rotundal functions, and similar doses
will affect visual performance in such a way as to increase the probability
of an automobile or aircraft accident (9,10,19). However, threshold doses of
ethanol in our experiments were 0.05 ml/kg. This is really a very small
dose of ethanol, giving blood levels of about 0.005%, the equivalent
very roughly, of 0.3-0.4 ounces of whiskey in a 70-kg person but still
sufficient to distort visual integrative functions. Thus, it seems to this
author that current ideas and regulations concerning "safe" blood ethanol
levels for operators of aircraft and automobiles may have to be sertewel eX

"p Summary.

We have shown in this study that alcohol exerts differential effects
on discrete portions of the brain centers involved in the transfer of visual
information to interpretative cortical areas. Inasmuch as the relative
contribution of information arriving over each of these pathways to the
decision-making process and subsequent behavior is affected by learning and
experience, we may’have explained in part why activity patterns resulting
from visual stimuli are affected in an unpredictable manner by low doses of
alcohol. * The data also suggest that ethanol may impair visua] functions at
doses substantially below levels currently believed "safe."





1tiple-
0: 361-368,

27.

28.

29.

30.

31.

32.

33.

34,

Sprague, J. M., G. Berlucchi, and G. Rizzolatti: The Role of the
Superior Colliculus and Pretectum in Vision and Visually Guided
Behavior. Visual Centers in the Brain, Handbook of Sensory Physiology,
Vol. VII/3B, p. 27-102 (R. Jung, Ed.) Springer-Verlag, New York, 1973.

Tharp, V. K., Jr., 0. H. Rundell, Jr., B. K. Lester, and H. L. Williams:
Alcohol and Information Processing, PSYCHOPHARMACOLOGIA, 40:33-52, 1974,

Wayner, M. J., T. Ono, and D. Nolley: Effects of Ethyl Alcohol on
Central Neurons, PHARMACOL. BIOCHEM. BEHAV., 3:499-506, 1975.

Wilkinson, I. M. S.: Alcohol and Human Eye Movement, BRAIN, 97:785-
792, 1974.

Wilkinson, I. M. S.: The Influence of Drugs and Alcohol Upon Human
Eye Movement, PROC. ROY. SOC. MED., 69:479-480, 1976.

Von Wright, J. M., and V. Mikkonen: The Influence of Alcohol on the
Detection of Light Signals in Different Parts of the Visual Field,
SCAND. J. PSYCHOL, 11:167-175, 1970.

«Yew, D. T.: The Effects of Alcohol on the Visual Cells of the Chick,
ACTA ANAT. (Basel), 97(4):419-422, 1977.

Zunder, P. M.: Effects of Alcohol and Prediction Outcome on
Extrafoveal Signal Detection, INT. STUD. ALCOHOL, 38:392-402, 1977.



14.

15.

16.

17.

18.

19,

20,

21.

22.

23.

24,

25.

26.

a 1

Klemm, W. R., and R. E. Stevens: Alcohol Effects on EEG and Multiple- | 27.
Unit Activity in Various Brain Regions of Rats, BRAIN RES., 70:361-368,

1974,

Klemm, W. R., L. R. Dreyful, E. Forney, and M. A. Mayfield: Differential
Effects of Low Doses of Ethanol on the Impulse Activity in Various
Regions of the Limbic System, PSYCHOPHARMACOLOGY, 50:131-138, 1976.

28.

i
|
|
4
|
|
Klemm, W. R., C. G. Mallari, L. R. Dreyful, J, C. Fiske, E. Forney, and | 29.
J. A. Mikeska: Ethanol-Induced Régional and Dose-Response Differences |
in Multiple Unit Activity in Rabbits, PSYCHOPHARMACOLOGY, 49;235-244, |

i

|

|

1976. 30.

Moskowitz, H.: Alcohol and Backward Masking of Visual Information,
Q. J. STUD. ALCOHOL, 37:40-45, 1976. 31.

Moskowitz, H., and S. Sharma: Effects of Alcohol on Peripheral Vision
as a Function of Attention, HUM. FACTORS, 16:174-180, 1974. 32,
Moskowitz, H., K. Ziedman, and S. Sharma: Visual Search Behavior |
While Viewing Driving Scenes under the Influence of Alcohol and '
Marijuana, HUM. FACTORS, 18:417~431, 1976. | 33.,
Motter, B. C., and D. B. Lindsley: Response Properties of Cells in the
Nucleus Lateralis Posterior of the Cat Associated with Visual Orienta-
tion, NEUROSCIENCE ABSTRACTS, 3:570, 1977.

34,
Revzin, A. M.: Characteristics of the Spontaneous Electrical Activity f
in the Neostriatum of the Pigeon, FED. PROC., 24:338, 1965.

Revzin, A. M.:
of the Pigeon,

Some Characteristics of Wide-Field Units in the Brain
BRAIN BEHAV. EVOL., 3:195-204, 1970.

Revzin, A. M.: Effects of Organophosphate Pesticides and Other Drugs
on Subcortical Mechanisms of Visual Integration, AVIAT. SPACE ENVIRON.
MED., 47:627-629, 1976. .

,
Revzin, A. M., and H. J. Karten: Rostral Projections of the Optic
Tectum and Nucleus Rotundus in the Pigeon, BRAIN RES., 3:264-276, 1966.

Salvatore, S.: Response Speed on a Function of Sensory Pattern and
Alcohol in a Velocity Judgement Task, ERGONOMICS, 18:491-502, 1975.

Sekuler, R., and Karlene Ball: Mental Set Alters Visibility of
Moving Targets, SCIENCE, 198:60-62, 1977.

»



‘ton

o

may differentially affect functionally different inputs to the rotundal
cell (2) and also that spontaneous firing and stimulus-evoked fir: of
sensory projection cells may carry different kinds of informations The
cells in posterior rotundus are simpler in response than the anterior
rotundal units. They respond to any retinal image movement. Response
amplitude is largely independent of stimulus size, shape, direction of
movement, etc., although, within limits, increasing velocity of movement
does increase frequency of cell discharge. Ethanol (0.05-0.15 ml/kg)
increases the mean firing rate of these cells. The vigor the stimulus-
evoked response tends to follow spontaneous rate changes, (ie brief,
ethanol inhibits anterior rotundal,units, and it stimulates the posterior
rotundal cells at low dose levels]

A number of interesting conclusions derive from this differential
action. For example, there is some disagreement about effects of alcohol
on peripheral vision (18,32,34) and other perceptual functions (1,4,7).

This variability in the results of alcohol studies may well be, in part at
least, an unavoidable consequence of the way in which alcohol works in the
brain. Visual information is carried to many different areas of cortex over
a number of anatomigally distinct pathways. Each cortical area responds to
different, though overlapping, sets of pattern abstractions. from the retinal
image. Perception of an object, such as this paper, can be thought of as
resulting from parallel processing of some subset of the set of available
abstractions (6). Both the set of abstractions and the ways in which they
are combined for perception seem to be learned, at least in part (6) The
present evidence guggests that each functionally defined subset of visual
ones is differentially affected by alcohol in a dose-dependent way,

[tm » the information fed into the "parallel processor" will be distorted by
ethanol or will be erroneous in some ways] The extent to which the resultant
processor error can affect a visual function will depend on the number of
ethanol~sensitive abstraction subsets used in that particular visual
integration. The number and kind of subsets used for any visual perception
are functions of the entire stimulus configuration and the mental set of the
subject (26). These inevitably will differ considerably among individuals.
It follows that results from studies on the effects of alcohol on visual
perception must depend on the dose of alcohol used, the minutiae of stimulus
configuration and presentation, and the developmental backgrounds of the
subject population. Since no experiments can be identical in those ways,
the results of experiments on ethanol ingestion must, as suggested above,
differ--and this is an unavoidable consequence of the way ethanol acts in
the brain. . .

The dose-response characteristics of the neurones in anterior and
osterior rotundus and in "dorsal thalamus" differ rather considerably.

This suggests, as indicated above, that the effects of alcohol on any given
behavior are dose-dependent. Therefore, behavioral changes produced by

high dosdw of alcohol cannot, with any confidence, be extrapolated to lower
doses.j After all, behaviors mediated by dorsal thalamus will not be affected



|
H

EFFECTS OF ETHANOL ON VISUAL UNIT ACTIVITY IN THE THALAMUS

I. Introduction.
a
Ethyl alcohol impairs driving or flying performance in part through an

impairment in visual system function”(9,10,19). The mechanisms of such
ethanol-induced visual dysfunction are uncertain. Explanations include a
slowing of information processing in the brain (1 +25), impaired eye
movement control (9,30,31), slowed target tracking (7), and impaired
_peripheral vision Pk yas > among others 3334). Indeed, there is some
suggestion that visual functions need not be-imvélved at all; that ethanol
-impairs “outputting," or the ability of the brain to output appropriate
responses to a nfiguration (28). The visual functions
affected by éthanol, and, perhaps, evén outputting, are largely mediated by
retinal inputs to the superior colliculus (27) and the further collicular
projections to the posterior thalamus (8,20) and beyond. Thus, it seemed
likely that the behavioral effects of ethanol noted above could be explained,
and further effects predicted, by a selective action of ethanol on visual
neurones in the colliculo-cortical projection system. The present studies
were undertaken to test this hypothesis. In such an investigation it is
essential that drug effects be evaluated in terms of actions on sets of
neurones of specified characteristics, /Sinte we have shown that drug effects
may be limited to one small group of neurones, carrying specific messages,
within a larger neuronal aggregate forming a visual relay nucleus 3 (23). Our
prior work hae indicated that low doses of ethanol will inhibit spontaneous
activity of directionally selective neurones in the nucleus rotundus of the
pigeon (23). Rotundus is a visual relay nucleus in avian posterior thalamus.
It receives information from the optic tectum-superior colliculus and relays
it to telencephalon (24) and is thus at least functionally homologous to the
lateralis posterior/pulvinar complex in mammals (8,20). In the present study
we report differential effects of ethanol on functionally different neurone
systems in rotundus and overlying dorsal thalamus, and suggest: (i) that
such differential pharmacological specificity may be partly responsible for
the varying behavioral effects produced by ethanol; (41) that the effects of
ethanol on posterior thalamic visual functions can explain most of the
effects of ethanol om visual functions noted above; and (iii) that low doses
of alcohol may be more toxic or dangerous than is generally recognized.

II. Methods. Cr ne

Urethane-anesthetized white carneau ptgeons were used, since pigeons are
a useful and inexpensive model system for ethanol intoxication (11,23,33).
The dose of urethane used was usually 1.8 gm/kg, which was sufficient to block
eye movements for the 8~ to 12-hour duration of the experiments. The birds
were clamped in a special stereotactic apparatus built to permit virtually
unobstructgd access to the visual field of the left eye of the animal. Head
and electrode alignments were such that the Karten and Hodos atlas (13)

1


Technical Report Documentation Page

T. Report No. 2. Government Accession No. 3. Recipient's Catalog No.

@FAA-AM-78-2

‘4, Title and Subtitle 5. Report Date

6. Performing Organization Code

EFFECTS OF ETHANOL ON VISUAL UNIT ACTIVITY

IN THE THALAMUS @. Performing Orgonization Report No.
7. Authors)

A. M. Revzin

9. Performing Organization Nome ond Address 10. Work Unit No. (TRAIS)

FAA Civil Aeromedical Institute TT. Contact or Grant No.

P.O. Box 25082

Oklahoma City, Oklahoma 73125 13. Type of Report ond Period Covered

12. Sponsoring Agency Nome and Address
Office of Aviation Medicine
Federal Aviation Administration

800 Independence Avenue, S.W. T4. Sponsoring Agency Code
Washington, D.C. 20591 FAA

15. Supplementary Notes

This work was performed under tasks AM-A-76-TOX-30 and AM-A-77~TOX-30,.

16. Abstract

We studied the effects of ethanol on the spontaneous activity of single neurones

in functionally differentiated subnuclei of a posterior thalamic visual projection
area, nucleus rotundus, in the anesthetized pigeon. Low doses of ethanol, 0.05 -
0.10 m1/kg (producing blood levels of about 0.005 - 0.010%), inhibited activity

in anterior rotundus but had complex excitatory~inhibitory effects on posterior
rotundal cells. Nonvisual dorsal thalamic cells, and "lateral geniculate" neurones
were inhibited by ethanol but threshold doses {0.25 - 0.40 ml/kg) were far higher
than those for the rotundal cells (0.05 ml/kg). These differing dose-response
curves for visual and nonvisual thalamic neurones suggest: (1) Low doses of ethanol
may seriously impair peripheral visual functions; (11) The behavioral effects of

“\ ethanol are highly dose-dependent; (111) Effects of low doses of ethanol may not
Y be extrapolated from high-dose effects since high-dose effects may "mask" effects
q dominant at low doses; (iv) The effects of a given dose of ethanol may vary widely
3 and unpredictably, among individuals. Thus, the notorjous unpredictability of
M ethanol-induced changesyin behavior or task performance may be the inevitable
Ne consequence of the reported differential dose-response effects on single neurones,
2

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